| Identification | Back Directory | [Name]
6-Bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole | [CAS]
1231930-33-8 | [Synonyms]
Abemaciclib Impurity 1
6-Bromo-4-fluoro-1-isopropyl-2-methylbenzimidazole
6-bromo-4-fluoro-2-methyl-1-propan-2-ylbenzimidazole
6-Bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole
6-Bromo-4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazole
6-bromo-4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazole
1H-BenziMidazole, 6-broMo-4-fluoro-2-Methyl-1-(1-Methylethyl)-
6-Bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole ISO 9001：2015 REACH | [EINECS(EC#)]
807-019-0 | [Molecular Formula]
C11H12BrFN2 | [MDL Number]
MFCD16660227 | [MOL File]
1231930-33-8.mol | [Molecular Weight]
271 |
| Chemical Properties | Back Directory | [Boiling point ]
353.4±22.0 °C(Predicted) | [density ]
1.49 | [storage temp. ]
Sealed in dry,Room Temperature | [pka]
3.48±0.10(Predicted) | [Appearance]
Off-white to yellow Solid | [InChI]
InChI=1S/C11H12BrFN2/c1-6(2)15-7(3)14-11-9(13)4-8(12)5-10(11)15/h4-6H,1-3H3 | [InChIKey]
SJQZRZLUEGCXFN-UHFFFAOYSA-N | [SMILES]
C1(C)N(C(C)C)C2=CC(Br)=CC(F)=C2N=1 |
| Hazard Information | Back Directory | [Uses]
6-Bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole is a pharmaceutical intermediate. It can be used in the preparation of Abemaciclib, a kinase inhibitor for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer who have experienced disease progression following endocrine therapy and prior chemotherapy. | [Flammability and Explosibility]
Notclassified | [Synthesis]
The general procedure for the synthesis of 6-bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[D]imidazole using (E)-N-(4-bromo-2,6-difluorophenyl)-N'-isopropylacetamidine as starting material was as follows: potassium tert-butanolate (6.9 kg) was added batchwise to a (E)-N-(4-bromo-2,6-difluorophenyl)-N'-isopropylacetamidine (16.2 kg) N-methylformamide (76 kg) solution while controlling the reaction temperature below 30°C. The reaction mixture was heated to 70-75°C until the completion of the reaction was monitored by HPLC. The reaction solution was then cooled to 20-30°C and the reaction was quenched by addition of water (227 kg). Extraction was carried out with methyl tert-butyl ether (37 x 4 kg) and the combined organic phases were washed with brine (49 x 2 kg). The organic phase was concentrated to 25-30 L, n-hexane (64 kg) was added and the resulting slurry was filtered to give 6-bromo-4-fluoro-1-isopropyl-2-methyl-1H-benzo[D]imidazole (11 kg). Mass spectrum (ES+): m/z = 272 (M + H)+. For further purification, the crude product was dissolved in dichloromethane, filtered through silica gel and Celite pads, and finally recrystallized from a mixed solvent of methyl tert-butyl ether/hexane. | [References]
[1] Patent: US2010/160340, 2010, A1. Location in patent: Page/Page column 10
[2] Patent: WO2015/130540, 2015, A1. Location in patent: Page/Page column 22 |
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