Sodium Hydroxide → HCID 86586279, compound

HRID 897829Notes

Reaction equation

HRID 897829 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:33]3[CH:38]=[CH:37][C:36]([CH:39]=O)=[CH:35][CH:34]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12.Cl.Cl.[CH3:43][O:44][C:45](=[O:54])[C@H:46]([CH2:48][C:49]1[N:53]=[CH:52][NH:51][CH:50]=1)[NH2:47].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClC(Cl)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:33]3[CH:34]=[CH:35][C:36]([CH2:39][NH:47][C@@H:46]([CH2:48][CH:49]4[CH:50]=[N:51][CH:52]=[N:53]4)[C:45]([O:44][CH3:43])=[O:54])=[CH:37][CH:38]=3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:27])([F:28])[F:26])=[CH:21][C:20]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2×HCID 11444225N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide2×HCID 178419105HCID 178419105, compound2×

Product 1

HCID 86586279HCID 86586279, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide (Intermediate 2) (0.075 g, 0.14 mmol), L-histidine methyl ester dihydrochloride (0.046 g, 0.27 mmol), and sodium triacetoxyborohydride (0.087 g, 0.41 mmol) in dichloroethane (1.4 mL) was shaken at room temperature for 3 days. Additional portions of), L-histidine methyl ester dihydrochloride (0.100 g, 0.59 mmol) and sodium triacetoxyborohydride (0.085 g, 0.40 mmol) were added and the reaction mixture was shaken for 2 days. 1N NaOH (1 mL) was added and the brown precipitate was collected by filtration. The filtrate was extracted with dichloromethane (5 mL) and the organic extract was concentrated and combined with the aforementioned brown solid. The crude mixture was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 20-80% acetonitrile-0.05 M ammonium acetate over 25 min, 21 mL/min); the fraction eluting from 18.9-20.5 min was collected, concentrated, and lyopholized to afford methyl (2S)-2-({4-[4-amino-3-(4-{[2-fluoro-4-(trifluoromethyl)benzoyl]amino}-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]benzyl}amino)-3-(4H-4-imidazolyl)propanoate as a white solid. (0.029 g, 0.041 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.94 (1H, s), 8.35-8.38 (2H, m), 8.13 (2H, d, J=8.0 Hz), 7.99-8.02 (1H, m), 7.90 (1H, d, J=10.8 Hz), 7.75 (1H, d, J=8.4 Hz), 7.51 (1H, s), 7.39-7.45 (5H, m), 6.78 (1H, bs), 3.96 (3H, s), 3.82 (1H, d, J=14.0 Hz), 3.59 (3H, s), 3.47 (1H, t, J=6.4 Hz), 2.80-2.89 (2H, m), and 1.91 (3H, s); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 11.15 min. MS: MH+ 704.2.

Workup

  1. stirringthe reaction mixture was shaken for 2 days
  2. filtrationthe brown precipitate was collected by filtration
  3. extractionThe filtrate was extracted with dichloromethane (5 mL)
  4. extractionthe organic extract
  5. concentrationwas concentrated
  6. customThe crude mixture was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 20-80% acetonitrile-0.05 M ammonium acetate over 25 min, 21 mL/min)
  7. washthe fraction eluting from 18.9-20.5 min
  8. customwas collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9fb3fab6bdea4513b758495b30c01509
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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