Diisopropylethylamine → (2S,3S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester

HRID 737209Notes

Reaction equation

HRID 737209 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][C@H:13]([OH:16])[C@H:12]1[C:17]([OH:19])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[NH2:60][C:61]1[S:62][CH:63]=[C:64]([C:66]2[CH:77]=[CH:76][C:69]([C:70]([NH:72][CH:73]3[CH2:75][CH2:74]3)=[O:71])=[CH:68][CH:67]=2)[N:65]=1>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][C@H:13]([OH:16])[C@H:12]1[C:17](=[O:19])[NH:60][C:61]1[S:62][CH:63]=[C:64]([C:66]2[CH:67]=[CH:68][C:69]([C:70](=[O:71])[NH:72][CH:73]3[CH2:75][CH2:74]3)=[CH:76][CH:77]=2)[N:65]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54213972(2S,3S)-1-[(benzyloxy)carbonyl]-3-hydroxypyrrolidine-2-carboxylic acidHCID 866164294-(2-Amino-thiazol-4-yl)-n-cyclopropyl-benzamide trifluoroacetic acid salt

Product 1

HCID 57849874(2S,3S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-3-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S,3S)-3-Hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (41.9 mg, 1.6 mmol) and HATU (66.3 mg, 1.7 mmol) were dissolved in DMF (2 mL). DIEA (55 μL, 0.32 mmol) was then added, and the reaction was stirred at ambient temperature for 15 minutes. Then 4-(2-Amino-thiazol-4-yl)-N-cyclopropyl-benzamide trifluoroacetic acid salt (62.9 mg, 0.17 mmol) was added, and the reaction was stirred at ambient temperature overnight. The reaction was filtered and purified by reverse phase HPLC to give the desired product. Yield 11.8 mg. MS: 507.2 (M+H+); H1 NMR (DMSO-d6): δ(ppm) 0.50-77 (m, 4H), 1.70-2.10 (m, 2H), 4.20-4.40 (m, 1H), 4.86-5.17 (m, 2H), 7.00-7.42 (m, 4H), 7.74-8.01 (m, 5H), 8.40-8.48 (m, 1H), 12.58-12.67 (m, 1H).

Workup

  1. stirringthe reaction was stirred at ambient temperature overnight
  2. filtrationThe reaction was filtered
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-45d663fe358d4192bd8f752b7fe15eb9
Source dataset
uspto-grants-2009_09
Patent number
US07595398B2

Reaction notes

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