Acetic Acid → 1-{1-[4-(5-Methoxy-3-phenyl-1,6-naphthyridin-2-yl)benzyl]piperidin-4-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 604994Notes

Reaction equation

HRID 604994 reaction equation
[CH3:1][O:2][C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:7]([C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1)=[N:8]2.[NH:27]1[CH2:32][CH2:31][CH:30]([N:33]2[C:37]3=[N:38][CH:39]=[N:40][C:41]([NH2:42])=[C:36]3[CH:35]=[N:34]2)[CH2:29][CH2:28]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN(C=O)C.CO>[CH3:1][O:2][C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:7]([C:13]1[CH:14]=[CH:15][C:16]([CH2:17][N:27]3[CH2:32][CH2:31][CH:30]([N:33]4[C:37]5=[N:38][CH:39]=[N:40][C:41]([NH2:42])=[C:36]5[CH:35]=[N:34]4)[CH2:29][CH2:28]3)=[CH:19][CH:20]=1)=[N:8]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 577139461-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 598461374-(5-Methoxy-3-phenyl-1,6-naphthyridin-2-yl)benzaldehyde

Product 1

HCID 598461511-{1-[4-(5-Methoxy-3-phenyl-1,6-naphthyridin-2-yl)benzyl]piperidin-4-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(5-methoxy-3-phenyl-1,6-naphthyridin-2-yl)benzaldehyde (80 mg, 0.235 mmol) and 1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine-4-amine (58 mg, 0.26 mmol) in dry DMF (1 mL) containing acetic acid (70 μL, 1.25 mmol) was stirred at room temperature 16 hours. Sodium triacetoxyborohydride (91 mg, 0.43 mmol) was then added to the semi-solid mixture and stirred for three hours. The mixture was diluted with methanol and the solvent evaporated. The residue was purified by column chromatography on silica gel eluting with a 0.5 to 5% methanol/ethyl acetate (sat'd NH3) gradient. The combined fractions were concentrated and the residue was digested with acetonitrile to afford upon cooling the pure title compound. 1H-NMR (500 MHz, CDCl3): δ 8.55 (1H, s), 8.39 (1H, s), 8.23 (1H, d, J=6 Hz), 7.92 (1H, s), 7.56 (1H, d, J=6 Hz), 7.41 (2H, d, J=7.8 Hz), 7.24-7.33 (5H, m), 5.40 (2H, br s), 4.75 (1H, m), 4.17 (3H, s), 3.57 (2H, br s), 2.31-2.41 (2H, m), 2.18-2.28 (2H, m), 1.96 (2H, br d, J=10.7 Hz). m/e (m+1): 543.3.

Workup

  1. stirringstirred for three hours
  2. customthe solvent evaporated
  3. customThe residue was purified by column chromatography on silica gel eluting with a 0.5 to 5% methanol/ethyl acetate (sat'd NH3) gradient
  4. concentrationThe combined fractions were concentrated
  5. customto afford

Sources & evidence

ORD record
ord-4d6ee85a731c4d99b00573089ad18324
Source dataset
uspto-grants-2011_03
Patent number
US07910561B2

Reaction notes

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