2-Methoxyethylamine → HCID 22346933, compound

HRID 2056027Notes

Reaction equation

HRID 2056027 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](C=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.[CH3:41][O:42][CH2:43][CH2:44][NH2:45].[C:46](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]([CH2:46][NH:45][CH2:44][CH2:43][O:42][CH3:41])=[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:28])([F:27])[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 80182-MethoxyethylamineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 11444225N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide2×

Product 1

HCID 22346933HCID 22346933, compoundYield 11.4%

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), 2-methoxyethylamine (0.018 g, 0.24 mmol), and sodium triacetoxyborohydride (0.106 g, 0.500 mmol) in dichloroethane (1.4 mL) was shaken at room temperature for 24 h. 1N NaOH (1 mL) was added and the reaction mixture was concentrated, dissolved in DMF (2 mL), filtered through a syringe-tip Acrodisc filter, and 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 15.0-16.2 min was collected, concentrated, and lyopholized to afford N1-{4-[4-amino-1-(4-{[(2-methoxyethyl)amino]methyl}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a white solid (0.010 g, 0.016 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.94 (1H, d, J=4.0 Hz), 8.35-8.37 (2H, m), 8.16 (2H, d, J=8.0 Hz), 8.01 (1H, t, J=7.4 Hz), 7.90 (1H, d, J=10.0 Hz), 7.75 (1H, d, J=8.0 Hz), 7.52 (2H, d, J=8.0 Hz), 7.45 (1H, s), 7.40 (1H, d, J=8.8 Hz), 3.96 (3H, s), 3.80 (2H, s), 3.42-3.45 (2H, m), 3.25 (2H, m), and 2.70-2.71 (2H, m); 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 10.23 min. MS: MH+610.2.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutiondissolved in DMF (2 mL)
  3. filtrationfiltered through a syringe-tip Acrodisc
  4. filtrationfilter
  5. custompurified 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)
  6. washthe fraction eluting from 15.0-16.2 min
  7. customwas collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b759055b5993451ba165f66ae29e0503
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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