Acetyl chloride → HCID 58914729, compound

HRID 1297771Notes

Reaction equation

HRID 1297771 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:26]3[CH:31]=[C:30]([CH3:32])[C:29]([O:33][CH3:34])=[C:28]([CH3:35])[CH:27]=3)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:9]2=[O:25])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:45](Cl)(=[O:47])[CH3:46]>C(Cl)Cl>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][N:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:45](=[O:47])[CH3:46])=[CH:3][CH:4]=2)([C:26]2[CH:27]=[C:28]([CH3:35])[C:29]([O:33][CH3:34])=[C:30]([CH3:32])[CH:31]=2)[C:9]1=[O:25]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 58914741HCID 58914741, compound

Product 1

HCID 58914729HCID 58914729, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Combine 3-(4-amino-phenyl)-1-(2-chloro-benzyl)-3-(4-methoxy-3,5-dimethyl-phenyl)-1,3-dihydro-indol-2-one (126 mg, 0.26 mmol), N,N-diisopropylethylamine (0.068 mL, 0.39 mmol) and acetyl chloride (0.020 mL, 0.29 mmol) in CH2Cl2 (1 mL) and stirred at room temperature for 48 h. Dilute with CH2Cl2 and wash with water. Backwash water with CH2Cl2 and ethyl acetate. Combine all organics, dilute with more CH2Cl2 and wash with 1N HCl and brine. Dry (MgSO4), filter and concentrate in vacuo to give a residual foam. Purify by flash chromatography (gradient of 33% EtOAc/hexanes to 66% EtOAc/hexanes) to give 129 mg (67%) of the title compound as a white foam. MS (ES): m/z=525 (M+1), 523 (M−1); 1H NMR(DMSO-d6): δ9.99 (s, 1H), 7.53 (m, 3H), 7.41-7.26 (m, 4H), 7.12 (m, 3H), 6.98 (m, 2H), 6.82 (s, 2H), 5.08 (s, 2H), 3.64 (s, 3H), 2.15 (s, 6H).

Workup

  1. washwash with water
  2. additionCombine all organics, dilute with more CH2Cl2
  3. washwash with 1N HCl and brine
  4. dry with materialDry (MgSO4)
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customto give a residual foam
  8. customPurify by flash chromatography (gradient of 33% EtOAc/hexanes to 66% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8465a8941d3442af833da7b9032fe2d5
Source dataset
uspto-grants-2007_07
Patent number
US07250442B2

Reaction notes

Loading…