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Sodium Carbonate → 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432182
Notes
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Reaction equation

HRID 432182 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([N:11]3[C:15]4=[N:16][CH:17]=[N:18][C:19]([NH2:20])=[C:14]4[C:13](I)=[N:12]3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.CC1(C)C(C)(C)OB([C:30]2[CH:42]=[CH:41][C:33]([O:34][C:35]3[N:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[CH:32][CH:31]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>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>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([N:11]3[C:15]4=[N:16][CH:17]=[N:18][C:19]([NH2:20])=[C:14]4[C:13]([C:30]4[CH:42]=[CH:41][C:33]([O:34][C:35]5[N:36]=[CH:37][CH:38]=[CH:39][N:40]=5)=[CH:32][CH:31]=4)=[N:12]3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 223467854-(Pyrimidin-2-yloxy)phenylboronic acid pinacol esterHCID 223470211-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine3×

Product 1

HCID 223470101-(1,4-dioxaspiro[4.5]dec-8-yl)-3-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amineYield 75.7%

Reagents, catalysts & solvents 3

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 962WaterSolvent
HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(1,4-dioxaspiro[4,5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Intermediate N) (1.50 g, 0.00374 mol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-pyrimidine (intermediate BA) (1.23 g, 0.00412 mol), tetrakis(triphenylphosphine)palladium(0) (0.26 g, 0.00022 mol) and sodium carbonate (0.993 g, 0.00937 mol) in 40 mL 1,2-dimethoxyethane and 20 mL water was heated at 80° C. for eighteen hours, after which time additional 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.15 g, 0.00037 mol) was added. The mixture was stirred for an additional hour and then allowed to cool to ambient temperature. The precipitate was filtered and washed with 1,2-dimethoxyethane and dried in vacuo, to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-[4-(2-pyrimidinyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (1.26 g, 0.00283 mol): 1H NMR (DMSO-d6, 400 MHz) 8.68 (d, 2H), 8.254 (s, 1H), 7.73 (d, 2H), 7.37 (d, 2H), 7.31 (t, 1H), 6.30-7.20 (bs, 2H), 4.78-4.84 (m, 1H), 3.91 (s, 4H), 2.22-2.30 (m, 2H), 1.73-1.92 (m, 6H).

Workup

  1. temperatureto cool to ambient temperature
  2. filtrationThe precipitate was filtered
  3. washwashed with 1,2-dimethoxyethane
  4. customdried in vacuo

Sources & evidence

ORD record
ord-d54763f10a234a5ca5861e88a5c63579
Source dataset
uspto-grants-2003_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06660744B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes