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

HRID 737166노트

반응식

HRID 737166 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-d956d67c7ac74080b6f980c868ca319c
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07595398B2

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