1,2-Dimethoxyethane → 1-(1-benzyl-4-piperidinyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 897422Notes

Reaction equation

HRID 897422 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([NH2:23])=[C:17]3[C:16](Br)=[N:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:25]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([NH2:23])=[C:17]3[C:16]([C:35]3[CH:36]=[CH:37][C:32]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:33][CH:34]=3)=[N:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acid2×HCID 111534161-(1-benzyl-4-piperidinyl)-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine2×

Product 1

HCID 98262731-(1-benzyl-4-piperidinyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 50.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-(1-benzyl-4-piperidinyl)-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate D) (4.3 g, 11.10 mmol), 4-phenoxyphenylboronic acid (Intermediate V) (2.61 g, 12.21 mmol), palladium tetrakistriphenyphosphine(0.77 g, 0.67 mmol) and sodium carbonate(2.82 g, 26.65 mmol) were mixed with ethylene glycol dimethyl ether(100 ml) and water(50 ml). The reaction mixture was heated to reflux overnight. Organic solvent was removed and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed, dried and evaporated. The residue was purified via flash column chromatography using ethyl acetate/methanol (98/2) as mobile phase to give 2.65 g of 1-(1-benzyl-4-piperidinyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (CDCl3) 1.99(d, J=11.02 Hz, 2H), 2.25(m, 2H), 2.47 (m, 2H), 3.07(d, J=11.12 Hz), 3.59(s, 2H), 4.80(m, 1H), 5.52(s, 2H), 7.07(d, J=0.67, 1H), 7.15(m, 3H), 7.37(m, 6H), 7.66(d, J=8.51, 2H), 8.37(s, 1H); LC/MS (MH+=477).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux overnight
  3. customOrganic solvent was removed
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layer was washed
  6. customdried
  7. customevaporated
  8. customThe residue was purified via flash column chromatography

Sources & evidence

ORD record
ord-67afd832669b459c95b8edbef5a23216
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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