2-(4-bromo-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine → [bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-6,6-difluoro-5-{2-fluoro-5-[1-(5-trifluoromethyl-pyridin-2-yl)-1H-imidazol-4-yl]-phenyl}-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl)-amine

HRID 331162Notes

Reaction equation

HRID 331162 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[CH2:26][O:27][C:28]([CH3:51])([CH3:50])[C:29]([F:49])([F:48])[C@:30]([C:33]3[CH:38]=[C:37](B4OCC(C)(C)CO4)[CH:36]=[CH:35][C:34]=3[F:47])([CH3:32])[N:31]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.Br[C:53]1[N:54]=[CH:55][N:56]([C:58]2[CH:63]=[CH:62][C:61]([C:64]([F:67])([F:66])[F:65])=[CH:60][N:59]=2)[CH:57]=1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[CH2:26][O:27][C:28]([CH3:51])([CH3:50])[C:29]([F:48])([F:49])[C@:30]([C:33]3[CH:38]=[C:37]([C:53]4[N:54]=[CH:55][N:56]([C:58]5[CH:63]=[CH:62][C:61]([C:64]([F:67])([F:66])[F:65])=[CH:60][N:59]=5)[CH:57]=4)[CH:36]=[CH:35][C:34]=3[F:47])([CH3:32])[N:31]=2)([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:5][CH:4]=1

Participants

3

Reactant 2

HCID 683804802-(4-bromo-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridineHCID 68380558[bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-5-[5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-fluoro-phenyl]-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl}-amine

Product 1

HCID 86671888[bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-6,6-difluoro-5-{2-fluoro-5-[1-(5-trifluoromethyl-pyridin-2-yl)-1H-imidazol-4-yl]-phenyl}-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl)-amineYield 25.3%

Procedure

Reaction of [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-5-[5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2-fluoro-phenyl]-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl}-amine (intermediate B10.1) (300 mg, 380 μmol) with 2-(4-bromo-1H-imidazol-1-yl)-5-(trifluoromethyl)pyridine (111 mg, 380 μmol) yielded the [bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-6,6-difluoro-5-{2-fluoro-5-[1-(5-trifluoromethyl-pyridin-2-yl)-1H-imidazol-4-yl]-phenyl}-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl)-amine (77 mg, 25% yield) as a yellow foam. MS (ISP): m/z=800.3 [M+H]+.

Sources & evidence

ORD record
ord-d684fcbbf93e414f9a0c9a33b51307bb
Source dataset
uspto-grants-2014_11
Patent number
US08877744B2

Reaction notes

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