Tetrahydrofuran → HCID 68379926, compound

HRID 331156Notes

Reaction equation

HRID 331156 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.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

Participants

6

Reactant 4

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

Product 1

HCID 68379926HCID 68379926, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-0ab81054ca504cdb849d368e529a91dd
Source dataset
uspto-grants-2014_11
Patent number
US08877744B2

Reaction notes

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