Cesium carbonate → HCID 10008037, compound

HRID 2267641Notes

Reaction equation

HRID 2267641 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-d96ec8be19d640709968f5b52edc0aba
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

Loading…