Ammonium formate → HCID 178520357, compound

HRID 1630279Notes

Reaction equation

[NH:1]1[CH:5]=[C:4]([CH2:6][C:7]([NH:9][C@@H:10]([CH2:27][O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21]3[S:22][C:23](Br)=[CH:24][N:25]=3)=[CH:16][CH:15]=2)=[O:12])=[O:8])[N:3]=[CH:2]1.C([O-])=O.[NH4+]>[Pd].CO>[NH:1]1[CH:5]=[C:4]([CH2:6][C:7]([NH:9][C@@H:10]([CH2:27][O:28][CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[CH:18][CH:19]=2)=[O:12])=[O:8])[N:3]=[CH:2]1

Participants

Conditions

Temperature: 70 °C

Procedure

A flask was charged with (S)-2-(2-(1H-imidazol-4-yl)acetamido)-3-(benzyloxy)-N-(4-(5-bromothiazol-2-yloxy)phenyl)propanamide (25 mg, 0.045 mmol), prepared as in Example 1, methanol (20 mL), ammonium formate (300 mg, 4.84 mmol), and palladium on carbon (10%, 100 mg) and the mixture was heated at 70° C. for 30 minutes. The mixture then was cooled to ambient temperature and filtered. Product was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)) and then further purified by reverse phase HPLC to provide Compound 206, (S)-2-(2-(1H-imidazol-4-yl)acetamido)-3-(benzyloxy)-N-(4-(thiazol-2-yloxy)phenyl)propanamide (10.6 mg, 51%), as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.35 (s, 1H), 8.43 (d, J=6.4 Hz, 1H), 7.68 (d, J=11.2 Hz, 2H), 7.60 (s, 1H), 7.31-7.23 (m, 8H), 6.95 (s, 1H), 4.70-4.64 (m, 1H), 4.49 (s, 2H), 4.14-4.09 (m, 2H), 3.69-3.63 (m, 2H). MS (EI) for C24H23N5O4S. found 478.2 (MH+).

Workup

temperatureThe mixture then was cooled to ambient temperature
filtrationfiltered
customProduct was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1))
customfurther purified by reverse phase HPLC

Sources & evidence

ORD record: ord-c5569bab822a441db4acfcd7c53dc4eb
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791102B2

Reaction notes

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