Diisopropylethylamine → 2-[((S)-1-Benzyloxycarbonyl-pyrrolidine-2-carbonyl)-amino]-4-(4-cyclopropylcarbamoyl-phenyl)-thiazole-5-carboxylic acid methyl ester

HRID 737202Notes

Reaction equation

HRID 737202 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:35])NC1SC(C2C=CC=C(C(=O)NC3CC3)C=2)=CN=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][O:37][C:38]([C:40]1[S:44][C:43]([NH2:45])=[N:42][C:41]=1[C:46]1[CH:51]=[CH:50][C:49]([C:52](=[O:57])[NH:53][CH:54]2[CH2:56][CH2:55]2)=[CH:48][CH:47]=1)=[O:39].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.C(OC(N1CCC[C@H]1C(O)=O)=O)C1C=CC=CC=1>>[CH3:36][O:37][C:38]([C:40]1[S:44][C:43]([NH:45][C:16]([C@@H:12]2[CH2:13][CH2:14][CH2:15][N:11]2[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])=[O:35])=[N:42][C:41]=1[C:46]1[CH:47]=[CH:48][C:49]([C:52](=[O:57])[NH:53][CH:54]2[CH2:56][CH2:55]2)=[CH:50][CH:51]=1)=[O:39]

Participants

6

Reactant 5

HCID 81531DiisopropylethylamineHCID 101987Benzyloxycarbonyl-L-prolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57849886(S)-2-[5-(3-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl esterHCID 866164452-Amino-4-(4-cyclopropylcarbamoyl-phenyl)-thiazole-5-carboxylic acid methyl ester

Product 1

HCID 578496712-[((S)-1-Benzyloxycarbonyl-pyrrolidine-2-carbonyl)-amino]-4-(4-cyclopropylcarbamoyl-phenyl)-thiazole-5-carboxylic acid methyl ester

Procedure

In a similar procedure as described for the synthesis of Compound 5312 (Example 312), 2-amino-4-(4-cyclopropylcarbamoyl-phenyl)-thiazole-5-carboxylic acid methyl ester (0.098 g, 0.31 mmol) was treated with HATU (0.18 g, 0.46 mmol), DIEA (0.3 mL, 2.3 mmol), and (S)-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester (0.12 g, 0.46 mmol) to furnish the desired product. 1HNMR (DMSO-d6) δ(ppm)12.90-12.88 (d, 1H), 8.89-8.85 (m, 1H), 8.51-8.50 (d, 1H), 7.86-7.72 (m, 4H), 7.37-7.33 (m, 2H), 7.15-7.09 (m, 2H), 5.09-4.87 (m, 2H), 4.51-4.49 (m, 1H), 3.74-3.72 (m, 3H), 3.53-3.47 (m, 1H), 2.88-2.84 (m, 1H), 2.45 (m, 1H), 1.91-1.87 (m, 3H), 0.71-0.59 (m, 4H); MS: 549.2 (M+H+).

Sources & evidence

ORD record
ord-87149e005a804700b2cdf33eaa433719
Source dataset
uspto-grants-2009_09
Patent number
US07595398B2

Reaction notes

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