Dicyclohexylcarbodiimide → 3-methoxy-5-(N-carbobenzyloxy-L-phenylalanyl-L-alaninamido)-[1,2,4]thiadiazole

HRID 992249ノート

反応式

HRID 992249 の反応式
[NH2:1][C:2]1[S:6][N:5]=[C:4]([O:7][CH3:8])[N:3]=1.[C:9]([NH:19][C@H:20]([C:28]([NH:30][C@H:31]([C:33](O)=[O:34])[CH3:32])=[O:29])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH3:8][O:7][C:4]1[N:3]=[C:2]([NH:1][C:33](=[O:34])[C@H:31]([CH3:32])[NH:30][C:28](=[O:29])[C@H:20]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[NH:19][C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[S:6][N:5]=1

参加物

7

反応物 5

HCID 10868Dicyclohexylcarbodiimide2 回HCID 757711-HydroxybenzotriazoleHCID 152128N-Benzyloxycarbonylphenylalanylalanine2 回HCID 3141795-Amino-3-methoxy-1,2,4-thiadiazoleHCID 27960291-Hydroxybenzotriazole hydrate

生成物 1

HCID 120523903-methoxy-5-(N-carbobenzyloxy-L-phenylalanyl-L-alaninamido)-[1,2,4]thiadiazole

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-amino-3-methoxy-[1,2,4]thiadiazole (0.37 g, 2.8 mmol) and N-carbobenzyloxy-L-phenylalanyl-L-alanine, N-Cbz-Phe-Ala-OH, (1.0 g, 2.7 mmol) in DMF (25 mL) was added 1,3-dicyclohexylcarbodiimide, DCC, (0.56 g, 2.7 mmol). After stirring for 30 min, 1-hydroxybenzotriazole hydrate, HOBT, (0.36 g, 2.7 mmol) was added and the resulting mixture was stirred at room temperature for 20 h. Volatile materials were removed in vacuo and the residue was purified by column chromatography on silica gel using a solvent mixture of dichloromethane and methanol (96/4) thereby affording the title compound as a white solid (1.2 g). Further purification by cristallization and chromatography on silica gel gave 3-methoxy-5-(N-carbobenzyloxy-L-phenylalanyl-L-alaninamido]-[1,2,4]thiadiazole (0.87 g, 67% yield). M.p. 161-162° C.; 1H-NMR (CDCl3) 7.14-7.38 (m, 12H, 10Ar—H and 2 NH), 5.92 (br. s, 1H, NH), 5.06 (s, 2H, OCH2), 4.38 (m, 1H, CHCH2Ar), 4.00 (m, 1H, CHCH3), 3.97 (s, 3H, OMe), 3.00-3.08 (m, 2H, CHCH2Ar), 1.34 (d, J=8.9 Hz, 3H, Me); MS (m/z) 484 (M++1), 416, 361, 316, 285, 185, 132, 75. The latter compound was also prepared by using diphenylphosphoryl azide and triethylamine instead of DCC/HOBT in 27.7% yield.

後処理

  1. stirringthe resulting mixture was stirred at room temperature for 20 h
  2. customVolatile materials were removed in vacuo
  3. customthe residue was purified by column chromatography on silica gel using
  4. additiona solvent mixture of dichloromethane and methanol (96/4)

出典と根拠

ORDレコード
ord-8936cf478bbe42afa4f062fa1f2c4688
出典データセット
uspto-grants-2002_10
特許番号
US06468977B1

反応ノート

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