Benzyl chloroformate → (S)-2-[4-(4-Cyclopropylcarbamoyl-phenyl)-thiazol-2-ylcarbamoyl]-thiazolidine-3-carboxylic acid benzyl ester

HRID 737186Notes

Reaction equation

[CH:1]1([NH:4][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([NH:18][C:19]([C@H:21]4[NH:25][CH2:24][CH2:23][S:22]4)=[O:20])[S:16][CH:17]=3)=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Cl[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37]>CN(C=O)C>[CH2:39]([O:38][C:36]([N:25]1[CH2:24][CH2:23][S:22][C@H:21]1[C:19](=[O:20])[NH:18][C:15]1[S:16][CH:17]=[C:13]([C:10]2[CH:9]=[CH:8][C:7]([C:5](=[O:6])[NH:4][CH:1]3[CH2:3][CH2:2]3)=[CH:12][CH:11]=2)[N:14]=1)=[O:37])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of (S)-thiazolidine-2-carboxylic acid [4-(4-cyclopropylcarbamoyl-phenyl)-thiazol-2-yl]-amide (50 mg, 0.13 mmol) in DMF (1 mL) was cooled to 0° C. DIEA (35 μL, 0.20 mmol) was added followed by benzyl chloroformate (30 μL, 0.21 mmol). The reaction was stirred at 0° C. and allowed to warm to ambient temperature over 2 hours. The reaction was filtered and purified by reverse phase HPLC to give the desired product. Yield 36.9 mg. MS: 509.1 (M+H+); H1 NMR (DMSO-d6): δ(ppm) 0.55-0.74 (m, 4H), 2.80-2.91 (m, 1H), 3.10-3.27 (m, 2H), 3.65-3.75 (m, 1H), 3.90-4.04 (m, 1H), 4.94-5.17 (m, 2H), 5.51-5.55 (s, 1H), 7.06-7.41 (m, 5H), 7.79-7.98 (m, 5H), 8.41-8.48 (d, 1H), 12.50-12.60 (m, 1H).

Workup

temperatureto warm to ambient temperature over 2 hours
filtrationThe reaction was filtered
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-ec398491d64e401796ada5423c83fce6
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595398B2

Reaction notes

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