Formaldehyde → 4-(3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanylmethyl)-1-methyl-4-piperidinol

HRID 432357Notes

Reaction equation

HRID 432357 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:27][N:26]([CH2:28][C:29]4([OH:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:13][CH:12]=3)[C:3]=12.C=O.[C:38](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:24]3[CH2:27][N:26]([CH2:28][C:29]4([OH:35])[CH2:34][CH2:33][N:32]([CH3:38])[CH2:31][CH2:30]4)[CH2:25]3)[N:9]=[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:15][CH:16]=3)[C:3]=12

Participants

5

Reactant 3

HCID 712Formaldehyde2×HCID 5049666Sodium triacetoxyborohydrideHCID 223472734-(3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanylmethyl)-4-piperidinol

Product 1

HCID 223470314-(3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanylmethyl)-1-methyl-4-piperidinolYield 55.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 4-(3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanylmethyl)-4-piperidinol (0.035 g, 0.000074 mol) and formaldehyde (0.006 mL, 37% in water, 0.000082 mol) in dichloroethane (4 mL) was stirred at room temperature under an atmosphere of nitrogen for one hr. Sodium triacetoxyborohydride (0.022 g, 0.000104 mol) was added into the mixture and stirred at ambient temperature under an atmosphere of nitrogen for eighteen hours. Molecular sieves (0.05 g, 3A, 4-8 mesh) and additional formaldehyde (0.006 mL, 37% in water, 0.000082 mol) was added and the reaction mixture was stirred at room temperature for eighteen hours. The solvent was removed under reduced pressure, and the residue was purified by RP-HPLC (Hypersil HS C18, 8 μm, 250×21.1 mm; 5%-100% over 25 min with 0.1 M ammonium acetate, 21 mL/min) to yield 4-(3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-azetanylmethyl)-1-methyl-4-piperidinol (0.020 g, 0.000041 mol).

Workup

  1. stirringstirred at ambient temperature under an atmosphere of nitrogen for eighteen hours
  2. stirringthe reaction mixture was stirred at room temperature for eighteen hours
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by RP-HPLC (Hypersil HS C18, 8 μm, 250×21.1 mm; 5%-100% over 25 min with 0.1 M ammonium acetate, 21 mL/min)

Sources & evidence

ORD record
ord-f9c3ff3017e443a2a8e54857aa04fa87
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

Loading…