Cesium carbonate → HCID 10008037, compound

HRID 1593303Notes

Reaction equation

HRID 1593303 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][C@H:13]([C:15]([NH:17][C@@H:18]2[C:24](=[O:25])[NH:23][C:22]3[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:21]=3[O:20][C@@H:19]2[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:16])[CH3:14])=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.Br[CH2:39][CH:40]1[CH2:42][CH2:41]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH:40]1([CH2:39][N:23]2[C:22]3[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:21]=3[O:20][C@H:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C@H:18]([NH:17][C:15](=[O:16])[C@H:13]([CH3:14])[NH:12][C:10](=[O:11])[CH2:9][C:4]3[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[CH:3]=3)[C:24]2=[O:25])[CH2:42][CH2:41]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 10029288HCID 10029288, compound

Product 1

HCID 10008037HCID 10008037, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N2-[(3,5-difluorophenyl)acetyl]-N1-[(2,3-cis)-7-methoxy-4-oxo-2-phenyl-2,3,4,5-tetrahydro-1,5-benzoxazepin-3-yl]-L-alaninamide (68) (95 mg, 0.186 mmol) in DMF (1 mL) under nitrogen was added (bromomethyl)cyclopropane (70 mg, 0.518 mmol) and powdered cesium carbonate (170 mg, 0.521 mmol). The mixture was stirred overnight at ambient temperature then diluted with water and extracted with ethyl acetate. The residue obtained from the organic extract was purified by flash chromatography on silica gel eluting with diethyl ether to afford the title compound in a 1:1 mixture with the 2S,3R diastereomer (65 mg, 62%) as a white solid. TLC Rf=0.26 (diethyl ether). 1H NMR (300 MHz, CDCl3) δ0.23 (m, 1H), 0.37-0.65 (m, 3H), 1.07 (d 1.5H, J=7.0 Hz), 1.21)d, 1.5H, J=7.0 Hz), 3.43 (s, 1H), 3.47 (s, 1H), 3.83 (s, 3H), 4.09 (m, 1H), 4.25 (m, 1H), 5.05 (m, 1H), 5.61 (m, 1H), 5.89 (br d, 1H), 5.99 (br d, 1H), 6.20 (br t, 1H), 6.66-6.85 (m, 5H), 7.19 (d, 1H), 8.3 Hz), 7.30-7.42 (m, 6H). MS APCI, m/z=564 (M+1). LC/MS: 2.77 min.

Workup

  1. extractionextracted with ethyl acetate
  2. customThe residue obtained from the
  3. extractionorganic extract
  4. customwas purified by flash chromatography on silica gel eluting with diethyl ether

Sources & evidence

ORD record
ord-1d31f3df737b46efa5eb3092225acf2d
Source dataset
uspto-grants-2007_11
Patent number
US07294622B2

Reaction notes

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