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

HRID 2091966
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HRID 2091966 반응식
[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]
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참가 물질

5

반응물 2

HCID 2723923Ammonium formateHCID 70271434(R)-benzyl 3-hydroxy-1-(4-(2-(4-morpholino-phenylamino)pyrimidin-4-yl)phenylamino)-1-oxopropan-2-ylcarbamate

생성물 1

HCID 57991089(R)-2-amino-3-hydroxy-N-(4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)phenyl)propanamide수율 68%

시약·촉매·용매 2

HCID 9942167Palladium hydroxide촉매
HCID 887
Methanol
용매

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온도
60 °C

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-4198f0406dbb4db7a70dc3d7625200c0
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08440663B2

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