Water → 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432150Notes

Reaction equation

HRID 432150 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:21][CH2:20][C:15]3([O:19][CH2:18][CH2:17][O:16]3)[CH2:14][CH2:13]2)[N:3]=1.[O:22]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C(COC)OC>[O:19]1[C:15]2([CH2:20][CH2:21][CH:12]([N:4]3[C:5]4=[N:6][CH:7]=[N:8][C:9]([NH2:11])=[C:10]4[C:2]([C:32]4[CH:33]=[CH:34][C:29]([O:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[CH:30][CH:31]=4)=[N:3]3)[CH2:13][CH2:14]2)[O:16][CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343774-Phenoxyphenylboronic acid2×HCID 223472163-bromo-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine2×

Product 1

HCID 223467671-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 87%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

3-bromo-1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (Intermediate X) (4.0 g, 11.3 mmol), 4-phenoxyphenylboronic acid (Intermediate V) (2.66 g, 12 mmol), sodium carbonate (2.87 g, 27 mmol), palladium tetrakis(triphenyphosphine) (0.78 g, 0.6 mmol) in dimethoxyethane (120 mL)/water (60 mL) mixture was heated at 85° C. under nitrogen for 4 hrs. Cool to room temperature and stand for 72 hrs. The solid which precipitated was filtered and washed with water and diethylether (100 mL of each). Dry in vacuo for 3 hrs to furnish 4.2 g of 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine as a beige solid (87%). 1H NMR (400 MHz, d6-DMSO) 8.24 (1H, s), 7.67 (2H, m), 7.45 (2H, m), 7.19 (5H, m), 4.78 (1H, m), 3.90 (4H, m), 2.25 (2H, m), 1.71-1.84 (6H, m) Mass Spec.: MH+=444.2.

Workup

  1. customThe solid which precipitated
  2. filtrationwas filtered
  3. washwashed with water and diethylether (100 mL of each)
  4. customDry in vacuo for 3 hrs

Sources & evidence

ORD record
ord-0bf2f70ce81d4cb389b3d1a0e6ef004c
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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