Methanesulfonyl chloride → HCID 117668034, compound

HRID 1052975Notes

Reaction equation

HRID 1052975 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3([CH2:23][CH2:24][CH2:25][OH:26])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:5]([CH3:27])[O:4][N:3]=1.CCN(C(C)C)C(C)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl>[CH3:37][S:38]([O:26][CH2:25][CH2:24][CH2:23][C:10]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH3:27])[CH:8]=2)[NH:12][C:11]1=[O:16])(=[O:40])=[O:39]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86281772HCID 86281772, compound

Product 1

HCID 117668034HCID 117668034, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of compound 5-(3,5-dimethylisoxazol-4-yl)-3-(3-hydroxypropyl)-3-phenylindolin-2-one (0.72 g, 2.0 mmol), DIPEA (1.05 mL, 6.0 mmol), MsCl (250 mg, 2.2 mmol) in CH2Cl2 (20 mL) was stirred at 0° C. then gradually raised to RT overnight. The contents were diluted with CH2Cl2, washed with water (2×10 mL), and concentrated. The crude was purified with flash chromatography to afford compound 3-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)propyl methanesulfonate (575 mg, 65.3%). 1H NMR (400 MHz, DMSO-d6): δH 10.73 (s, 1H), 7.24-7.38 (m, 7H), 7.02 (d, J=8.0 Hz, 1H), 4.13-4.16 (m, 2H), 3.12 (s, 3H), 2.37 (s, 3H), 2.30-2.34 (m, 2H), 2.20 (s, 3H), 1.30-1.48 (m, 2H). To a stirred solution of 3-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)propyl methanesulfonate (440 mg, 1.0 mmol) in dry THF (10 mL) was successively added triethylamine (280 μl, 2.0 mmol) and morpholine (174 mg, 2.0 mmol) at room temperature. The reaction mixture was heated at 80° C. for 15 h and then water (10 mL) was added. The aqueous layer was extracted with dichloromethane (3×10 mL). The combined organic layers were dried over sodium sulfate and filtered. After concentration of the filtrate in vacuo, the residue was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH: 95/5) to afford compound (385 mg, 89.3%) as a white solid. 1H NMR (400 MHz, CDCl3): δH 7.88 (s, 1H), 7.28-7.39 (m, 5H), 7.14-7.16 (m, 1H), 7.08 (s, 1H), 7.02 (d, J=8.0 Hz, 1H), 3.76 (m, 4H), 2.45-2.55 (m, 5H), 2.37-2.39 (m, 4H), 2.22-2.29 (m, 5H), 1.54-1.55 (m, 2H). MS (ESI) m/e [M+1]+ 432.0.

Workup

  1. temperaturethen gradually raised to RT overnight
  2. washwashed with water (2×10 mL)
  3. concentrationconcentrated
  4. customThe crude was purified with flash chromatography

Sources & evidence

ORD record
ord-4d253828ac3540fea7d764377a5af97a
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

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