1,2-Dichloroethane → (R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamate

HRID 1811098노트

반응식

HRID 1811098 반응식
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27]3[C:19]=2[C:20]2[CH:21]=[CH:22][C:23]([C:33](O)=[O:34])=[CH:24][C:25]=2[NH:26]3)[CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:50][N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>C1COCC1.C(Cl)Cl.CN(C=O)C>[C:31]([C:28]1[C:27]2[NH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:33]([N:54]4[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]4)=[O:34])[CH:24]=3)[C:19]=2[C:18]([N:14]2[CH2:15][CH2:16][CH2:17][C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:13]2)=[CH:30][CH:29]=1)#[N:32]

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 66605842(R)-5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylic acid

생성물 1

HCID 86642947(R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamate수율 39.3%

시약·촉매·용매 1

HCID 86642945dichloromethane tetrahydrofuran DMF용매

실험 절차

Step 4 A solution of (R)-5-(3-(benzyloxycarbonylamino)piperidin-1-yl)-8-cyano-9H-carbazole-2-carboxylic acid (130 mg, 0.277 mmol), EDC (74.5 mg, 0.388 mmol), HOBT (59.5 mg, 0.388 mmol), and 1-methylpiperazine (0.092 mL, 0.832 mmol) in THF-DCM-DMF (4:1:1, 6 mL) was stirred at rt over a weekend. The mixture was concentrated and partitioned between EtOAc and NaHCO3 (aq). The organic phase was washed with brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 100:0 to 92.5:7.5 DCM-2 M methanolic ammonia) to provide (R)-benzyl 1-(1-cyano-7-(4-methylpiperazine-1-carbonyl)-9H-carbazol-4-yl)piperidin-3-ylcarbamate as a yellow solid (60 mg). 1H NMR (400 MHz, DMSO-d6) δ 12.31 (s, 1H) 8.09 (d, J=8.13 Hz, 1H) 7.82 (d, J=8.35 Hz, 1H) 7.64 (s, 1H) 7.49 (d, J=7.69 Hz, 1H) 7.24-7.40 (m, 6 H) 6.93 (d, J=8.35 Hz, 1H) 4.87-5.11 (m, 2H) 3.00-3.96 (m, 12H) 2.83 (s, 3H) 2.55-2.70 (m, 1H) 1.73-2.08 (m, 3H) 1.34-1.57 (m, 1H).). Mass spectrum m/z 551.2 (M+H)+.

후처리

  1. concentrationThe mixture was concentrated
  2. custompartitioned between EtOAc and NaHCO3 (aq)
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from 100:0 to 92.5:7.5 DCM-2 M methanolic ammonia)

출처 및 근거

ORD 기록
ord-068e6a015e4c4474ba2e04bcf7bc0d8d
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362065B2

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