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

HRID 737166Notes

Reaction equation

HRID 737166 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(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).

Workup

  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

Sources & evidence

ORD record
ord-d956d67c7ac74080b6f980c868ca319c
Source dataset
uspto-grants-2009_09
Patent number
US07595398B2

Reaction notes

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