Methyl iodide → HCID 68604619, compound

HRID 2267615Notes

Reaction equation

HRID 2267615 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11][C@H:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])[C@H:9]([NH:20][C:21](=[O:36])[C@H:22]([CH3:35])[NH:23][C:24](=[O:34])[CH2:25][C:26]3[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=3)[C:8](=[O:37])[NH:7][C:6]=2[CH:38]=1.[H-].[Na+].I[CH3:42]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11][C@H:10]([C:12]3[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=3[F:19])[C@H:9]([NH:20][C:21](=[O:36])[C@H:22]([CH3:35])[NH:23][C:24](=[O:34])[CH2:25][C:26]3[CH:27]=[C:28]([F:33])[CH:29]=[C:30]([F:32])[CH:31]=3)[C:8](=[O:37])[N:7]([CH3:42])[C:6]=2[CH:38]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10030827HCID 10030827, compound

Product 1

HCID 68604619HCID 68604619, compoundYield 83.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N1-[(2R,3R)-7-chloro-2-(2,5-difluorophenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl]-N2-[(3,5-difluorophenyl)acetyl]-L-alaninamide (92) (100 mg, 0.177 mmol) in DMF (800 uL) under nitrogen at ambient temperature was added sodium hydride powder (60% in mineral oil) (7 mg, 0.182 mmol). After 5 minutes, iodomethane (25 mg, 0.176 mmol) was added via micro-syringe. After stirring for 3½ hours, the reaction was carefully quenched with 1N aqueous HCl then diluted with water and extracted with ethyl acetate. The organic extracts were combined and evaporated. The residue was purified by flash chromatography on silica gel eluting first with 1:1 (v/v) hexanes:ethyl acetate and finally with ethyl acetate to afford the title compound (85 mg, 82%) as a white solid. 1H NMR (300 MHz, Acetone-d6) δ1.07 (d, 1.5H, J=7.0 Hz), 1.13 (d, 1.5H, J=7.0 Hz), 3.46-3.58 (m, 5H), 4.28 (m, 0.5H), 4.40 (m, 0.5H), 4.87 (m, 1H), 5.52 (m, 1H), 6.80-6.98 (m, 3H), 7.11-7.26 (m, 3H), 7.33 (m, 0.5H), 7.40-7.51 (m, 2.5H), 7.70 (d, 1H, J=2.2 Hz), 7.81 (d, 1H, J=8.3 Hz). MS APCI, m/z=580 (M+1). LC/MS: 2.89 min.

Workup

  1. customthe reaction was carefully quenched with 1N aqueous HCl
  2. additionthen diluted with water
  3. extractionextracted with ethyl acetate
  4. customevaporated
  5. customThe residue was purified by flash chromatography on silica gel eluting first with 1:1 (v/v) hexanes

Sources & evidence

ORD record
ord-54a1fd2fe5224eb6b0e10cb15aae8c65
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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