Tetrahydrofuran → HCID 68379926, 화합물

HRID 331156

반응식

HRID 331156 반응식
[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.O1CCCC1.Cl[C:58]1[O:59][C:60]2[CH:66]=[C:65]([Cl:67])[CH:64]=[CH:63][C:61]=2[N:62]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O>[CH3:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([C:9]([NH:24][C:25]2[CH2:26][O:27][C:28]([CH3:50])([CH3:51])[C:29]([F:49])([F:48])[C@:30]([C:33]3[CH:38]=[C:37]([C:58]4[O:59][C:60]5[CH:66]=[C:65]([Cl:67])[CH:64]=[CH:63][C:61]=5[N:62]=4)[CH:36]=[CH:35][C:34]=3[F:47])([CH3:32])[N:31]=2)([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:21][CH:20]=1

참가 물질

6

반응물 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 771752,6-DichlorobenzoxazoleHCID 68380558HCID 68380558, 화합물

생성물 1

HCID 68379926HCID 68379926, 화합물수율 44%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
85 °C

실험 절차

A dried pressure tube was consecutively charged with [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) (100 mg, 127 μmol), tetrahydrofuran (3 ml), 2,6-dichlorobenzo[d]oxazole (31.6 mg, 165 μmol), cesium carbonate (165 mg, 507 μmol) and water (1.5 ml). The tube was flushed with argon, thereafter [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (11 mg, 12.7 μmol) was added, the tube was sealed and the reaction mixture heated at 85° C. for 64 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 80:20 as the eluent. The [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-5-[5-(6-chloro-benzo oxazol-2-yl)-2-fluoro-phenyl]-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl}-amine (41 mg, 44% yield) was obtained as a white solid. MS (ISP): m/z=740.4 [M+H]+ and 742.3 [M+2+H]+.

후처리

  1. customThe tube was flushed with argon
  2. addition[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (11 mg, 12.7 μmol) was added
  3. customthe tube was sealed
  4. customFor the workup, the reaction mixture was evaporated at reduced pressure
  5. customthe residue directly purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 80:20 as the eluent

출처 및 근거

ORD 기록
ord-0ab81054ca504cdb849d368e529a91dd
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877744B2

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