Ammonium formate → (R)-2-amino-3-hydroxy-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)propanamide

HRID 2091966Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]([NH:32]C(=O)OCC1C=CC=CC=1)[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[N:14]=2)=[CH:9][CH:8]=1)=[O:5].C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[NH2:32][C@H:3]([CH2:2][OH:1])[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)=[CH:22][CH:21]=3)[N:14]=2)=[CH:9][CH:8]=1)=[O:5]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of (R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholinophenylamino)-pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate from the step above in MeOH (10 mL) was added Pd(OH)2 (134 mg) and ammonium formate (369 mg, 5.85). The mixture was heated at 60° C. for 2 hours, cooled down to room temperature, and filtered on Celite by eluting with MeOH. The filtrate was concentrated in vacuo and the residue was purified by preparatory HPLC (TFA). The TFA salt was removed by using basic resin to afford (R)-2-amino-3-hydroxy-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)propanamide 365 (346 mg, 68%). 1H-NMR (400 MHz, DMSO-d6): 9.39 (s, 1H), 8.44 (d, 1H), 8.13 (d, 2H), 7.83 (d, 2H), 7.67 (d, 2H), 7.29 (d, 1H), 6.94 pm (d, 2H), 4.94 (m, 1H), 3.75 (m, 4H), 3.60 (m, 2H), 3.46 (m, 1H), 3.05 (m, 4H); MS (EI) m/z for C23H26N6O3: 435.4 (MH+).

Workup

temperaturecooled down to room temperature
filtrationfiltered on Celite
washby eluting with MeOH
concentrationThe filtrate was concentrated in vacuo
customthe residue was purified by preparatory HPLC (TFA)
customThe TFA salt was removed

Sources & evidence

ORD record: ord-4198f0406dbb4db7a70dc3d7625200c0
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440663B2

Reaction notes

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