Acetonitrile → 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432165Notes

Reaction equation

HRID 432165 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:23]1[C:27]2([CH2:32][CH2:31][CH:30]([N:33]3[C:37]4=[N:38][CH:39]=[N:40][C:41]([NH2:42])=[C:36]4[C:35](I)=[N:34]3)[CH2:29][CH2:28]2)[O:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)C>[O:23]1[C:27]2([CH2:28][CH2:29][CH:30]([N:33]3[C:37]4=[N:38][CH:39]=[N:40][C:41]([NH2:42])=[C:36]4[C:35]([C:11]4[CH:10]=[N:9][C:8]([O:1][C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)=[CH:13][CH:12]=4)=[N:34]3)[CH2:31][CH2:32]2)[O:26][CH2:25][CH2:24]1

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 223467202-Phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 223470211-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine2×

Product 1

HCID 223471771-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 71.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Intermediate AG) (1.1 g, 0.0037 mol), 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate N) (1.29 g, 0.0032 mol), tetrakis(triphenylphosphine)palladium (0.22 g, 0.00019 mol) and sodium carbonate (0.85 g, 0.008 mol) was heated in a mixture of ethylene glycol dimethyl ether (40 mL) and water (20 mL) at 80° C. for 16 hours under an atmosphere of nitrogen. The mixture was allowed to cool to ambient temperature and ethylene glycol dimethyl ether was removed under reduced pressure. The precipitate was collected by filtration, washed with water once, acetonitrile twice and diethyl ether twice to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-(6-phenoxy-3-pyridyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine as an off-white solid (1.03 g, 0.0023 mol): 1H NMR (DMSO-d6, 400 MHz) 8.36 (s, 1H), 8.24 (s, 1H), 8.03 (d, 1H), 7.45 (t, 2H), 7.22 (m, 3H), 7.16 (d, 1H), 4.81 (m, 1H), 3.93 (s, 4H), 2.24 (m, 2H), 1.88 (m, 6H); MS: MH+445.

Workup

  1. customethylene glycol dimethyl ether was removed under reduced pressure
  2. filtrationThe precipitate was collected by filtration
  3. washwashed with water once

Sources & evidence

ORD record
ord-86a04719430541a8aab52791ad52852b
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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