Acetyl chloride → (S)-1-acetyl-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

HRID 708657Notes

Reaction equation

HRID 708657 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22](=[O:44])[NH:23][C@H:24]([C:40]([O:42][CH3:43])=[O:41])[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)=[CH:28][CH:27]=2)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:45]4[CH:50]=[CH:49][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:47][CH:46]=4)[CH2:15][NH:16]3)=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:61](Cl)(=[O:63])[CH3:62].C(N(CC)CC)C.C(OCC)(=O)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH:21]([C:22](=[O:44])[NH:23][C@H:24]([C:40]([O:42][CH3:43])=[O:41])[CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)=[CH:30][CH:31]=2)[CH2:20][C:19]2[CH:18]=[C:17]3[C:12]([O:13][C@@H:14]([C:45]4[CH:46]=[CH:47][C:48]([O:51][CH2:52][C:53]5[CH:58]=[CH:57][C:56]([Cl:59])=[C:55]([Cl:60])[CH:54]=5)=[CH:49][CH:50]=4)[CH2:15][N:16]3[C:61](=[O:63])[CH3:62])=[CH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 67250762(S)-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

Product 1

HCID 67250498(S)-1-acetyl-7-[(S)-2-(4'-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-7-[(S)-2-(4′-cyano-biphenyl-4-yl)-1-methoxycarbonyl-ethylcarbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6-carboxylic acid tert-butyl ester (85 mg) in DCM (5 mL) at 0° C. was treated with acetyl chloride, and triethylamine. The mixture was allowed to slowly warm to room temperature. After 3 hours, ethyl acetate was added and the organic layer was washed with 1N HCl. The organic layer was washed saturated sodium bicarbonate solution and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure to give the crude amide. The residue was purified by flash chromatography (using hexanes/ethyl acetate, from 70:30 to 55:45, as an eluent) to give the product (76 mg).

Workup

  1. washthe organic layer was washed with 1N HCl
  2. washThe organic layer was washed saturated sodium bicarbonate solution and brine
  3. dry with materialdried over sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customto give the crude amide
  6. customThe residue was purified by flash chromatography (

Sources & evidence

ORD record
ord-ad34ccb36d0441a8a0fc958b32ba4ef6
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

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