Triethylamine → (S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-azetidine-1-carboxylic acid benzyl ester

HRID 737166ノート

反応式

HRID 737166 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH2:13][C@H:12]1[C:15]([OH:17])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.FC(F)(F)C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O.FC(F)(F)C(O)=O.[NH2:50][C:51]1[S:52][CH:53]=[C:54]([C:56]2[CH:67]=[CH:66][C:59]([C:60]([NH:62][CH:63]3[CH2:65][CH2:64]3)=[O:61])=[CH:58][CH:57]=2)[N:55]=1>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH2:13][C@H:12]1[C:15](=[O:17])[NH:50][C:51]1[S:52][CH:53]=[C:54]([C:56]2[CH:57]=[CH:58][C:59]([C:60](=[O:61])[NH:62][CH:63]3[CH2:65][CH2:64]3)=[CH:66][CH:67]=2)[N:55]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 12088656(2S)-1-(Benzyloxycarbonyl)azetidine-2-carboxylic acidHCID 866164294-(2-Amino-thiazol-4-yl)-n-cyclopropyl-benzamide trifluoroacetic acid salt

生成物 1

HCID 57849888(S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-azetidine-1-carboxylic acid benzyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(S)-Azetidine-1,2-dicarboxylic acid 1-benzyl ester (45.7 mg, 0.19 mmol) was dissolved in DMF (1.5 mL). Triethylamine (53 μL, 0.38 mmol) and pentafluorophenyl trifluoroacetate (33 μL, 0.19 mmol) were added, and the reaction was stirred at ambient temperature for 30 minutes. Then 4-(2-Amino-thiazol-4-yl)-N-cyclopropyl-benzamide trifluoroacetic acid salt (62.9 mg, 0. 17 mmol) was added. The reaction was stirred at ambient temperature overnight and then heated to 70° C. for 4 hours. The reaction was cooled, filtered, and purified by reverse phase HPLC to give the desired product. Yield 7.2 mg. MS: 477.1 (M+H+); H1 NMR (DMSO-d6): δ(ppm) 0.50-0.85 (m, 4H), 2.10-2.30 (m, 1H), 2.48-2.62 (m, 1H), 2.78-2.90 (m, 1H), 3.80-4.07 (m, 2H), 4.80-5.13 (m, 3H), 7.07-7.42 (m, 4H), 7.78-7.99 (m, 5H), 8.40-8.47 (m, 1H), 12.40-12.58 (m, 1H).

後処理

  1. stirringThe reaction was stirred at ambient temperature overnight
  2. temperatureheated to 70° C. for 4 hours
  3. temperatureThe reaction was cooled
  4. filtrationfiltered
  5. custompurified by reverse phase HPLC

出典と根拠

ORDレコード
ord-d956d67c7ac74080b6f980c868ca319c
出典データセット
uspto-grants-2009_09
特許番号
US07595398B2

反応ノート

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