2-(Difluoromethoxy)aniline → [Bis-(4-methoxy-phenyl)-phenyl-methyl]-{(4R,5R)-4-[5-(2-difluoromethoxy-phenylamino)-2-fluoro-phenyl]-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amine

HRID 1626114Notes

Reaction equation

HRID 1626114 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C@H:28]([F:40])[C@:29]([C:32]3[CH:37]=[C:36](Br)[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=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.[F:41][CH:42]([F:51])[O:43][C:44]1[CH:50]=[CH:49][CH:48]=[CH:47][C:45]=1[NH2:46]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[O:26][CH2:27][C@H:28]([F:40])[C@:29]([C:32]3[CH:37]=[C:36]([NH:46][C:45]4[CH:47]=[CH:48][CH:49]=[CH:50][C:44]=4[O:43][CH:42]([F:41])[F:51])[CH:35]=[CH:34][C:33]=3[F:39])([CH3:31])[N:30]=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

Participants

3

Reactant 2

HCID 9346202-(Difluoromethoxy)anilineHCID 71008920[bis-(4-methoxy-phenyl)-phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine

Product 1

HCID 71008828[Bis-(4-methoxy-phenyl)-phenyl-methyl]-{(4R,5R)-4-[5-(2-difluoromethoxy-phenylamino)-2-fluoro-phenyl]-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amineYield 45%

Procedure

In a manner analogous to that described in Example 3 a), the amination of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(4R,5R)-4-(5-bromo-2-fluoro-phenyl)-5-fluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl]-amine (intermediate C4.3) with 2-(difluoromethoxy)aniline yielded the title compound (45% yield) as a pale yellow foam. MS (ISP): m/z=686.5 [M+H]+.

Sources & evidence

ORD record
ord-fad3f6cf2d1b479cbda3fa2486fb4b6d
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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