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

HRID 1811098

反応式

HRID 1811098 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 86642945dichloromethane tetrahydrofuran DMF溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-068e6a015e4c4474ba2e04bcf7bc0d8d
出典データセット
uspto-grants-2013_01
特許番号
US08362065B2

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