Diisopropylethylamine → Tert-butyl 4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)piperazine-1-carboxylate

HRID 1052963Notes

Reaction equation

HRID 1052963 reaction equation
Cl[C:2]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[C:12]([CH3:17])=[N:13][O:14][C:15]=3[CH3:16])[CH:9]=2)[NH:4][C:3]1=[O:18].CCN(C(C)C)C(C)C.[N:34]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>C1COCC1.O>[CH3:17][C:12]1[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][C:3](=[O:18])[C:2]3([N:37]2[CH2:36][CH2:35][N:34]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38]2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[C:15]([CH3:16])[O:14][N:13]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 862828633-Chloro-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-one

Product 1

HCID 117668248Tert-butyl 4-(5-(3,5-dimethylisoxazol-4-yl)-2-oxo-3-phenylindolin-3-yl)piperazine-1-carboxylateYield 96.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

676 mg (2.0 mmol) of 3-chloro-5-(3,5-dimethylisoxazol-4-yl)-3-phenylindolin-2-one and 774 mg (6.0 mmol) of DIPEA were dissolved in 20 ml of THF, after the addition of 774 mg (4.0 mmol) of tert-butyl piperazine-1-carboxylate, the reaction solution was stirred for 0.5 h at room temperature. Subsequently, the solution was diluted with water. The aqueous phase was extracted with CH2Cl2 (2×30 mL). The combined organic phases were washed with aqueous NaHCO3 and with water, dried and concentrated in vacuum. The resulting residue was purified by chromatography (eluent: CH2Cl2/MeOH=20/1) to give product (940 mg, 96%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δH 10.75 (s, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.25-7.38 (m, 6H), 6.98 (d, J=8.0 Hz, 1H), 3.27-3.29 (m, 4H), 2.47-2.38 (m, 4H), 2.36 (s, 3H), 2.18 (s, 3H), 1.35 (s, 9H). MS (ESI) m/e [M+1]+ 489.

Workup

  1. extractionThe aqueous phase was extracted with CH2Cl2 (2×30 mL)
  2. washThe combined organic phases were washed with aqueous NaHCO3 and with water
  3. customdried
  4. concentrationconcentrated in vacuum
  5. customThe resulting residue was purified by chromatography (eluent: CH2Cl2/MeOH=20/1)

Sources & evidence

ORD record
ord-6d0356e34bfb4b48a03aff0dc92f36d2
Source dataset
uspto-grants-2016_07
Patent number
US09393232B2

Reaction notes

Loading…