Morpholine → (1R,2R)-2-(4-chlorophenyl)-1'-(3-(morpholine-4-carbonyl)phenyl)spiro [cyclopropane-1,3'-indolin]-2'-one

HRID 1805341Notes

Reaction equation

HRID 1805341 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([C:19]4[CH:20]=[C:21]([CH:25]=[CH:26][CH:27]=4)[C:22](O)=[O:23])[C:11]3=[O:28])[CH2:9]2)=[CH:4][CH:3]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH:60]1[CH2:65][CH2:64][O:63][CH2:62][CH2:61]1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([C:19]4[CH:27]=[CH:26][CH:25]=[C:21]([C:22]([N:60]5[CH2:65][CH2:64][O:63][CH2:62][CH2:61]5)=[O:23])[CH:20]=4)[C:11]3=[O:28])[CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 53245851HCID 53245851, compound

Product 1

HCID 53245076(1R,2R)-2-(4-chlorophenyl)-1'-(3-(morpholine-4-carbonyl)phenyl)spiro [cyclopropane-1,3'-indolin]-2'-oneYield 60.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (1S,2S) and (1R,2R)-3-(2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)benzoic acid (117 mg, 0.3 mmol), O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU)(145 mg, 0.45 mmol), N,N-Diisopropylethylamine (DIPEA) (154 μL, 0.9 mmol) and morpholine (79 μL, 0.9 mmol) in DMF (2 mL) was stirred at room temperature for 14 hours. Purification by preparative HPLC gave desired product as a white solid (83 mg, 60%). LC/MS m/e calcd. for C27H23ClN2O3: 458, observed (M+H)+: 459.2 1H NMR (400 MHz, MeOD-d4) δppm 2.23-2.31 (m, 2 H) 3.28-3.32 (m, 1 H) 3.77 (br. s., 8 H) 6.16 (d, J=7.58 Hz, 1 H) 6.81 (t, J=7.58 Hz, 1 H) 6.93 (d, J=7.83 Hz, 1 H) 7.11-7.19 (m, 1 H) 7.26-7.33 (m, 2 H) 7.33-7.38 (m, 2 H) 7.56 (d, J=7.58 Hz, 1 H) 7.60-7.67 (m, 2 H) 7.68-7.76 (m, 1 H).

Workup

  1. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-e1c609daea7844e3b9da607a8a0f7157
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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