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

HRID 1805341노트

반응식

HRID 1805341 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  1. customPurification by preparative HPLC

출처 및 근거

ORD 기록
ord-e1c609daea7844e3b9da607a8a0f7157
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354443B2

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