Sodium Bicarbonate → HCID 178480956, compound

HRID 897503Notes

Reaction equation

HRID 897503 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH:36]=[CH:37][CH:38]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>O.COCCOC.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>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:34]=[C:35]([NH:39][C:40](=[O:46])[O:41][C:42]([CH3:44])([CH3:43])[CH3:45])[CH:36]=[CH:37][CH:38]=3)[C:10]=12

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 2735133Sodium Carbonate MonohydrateHCID 2773617tert-Butyl [3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 178481014HCID 178481014, compound

Product 1

HCID 178480956HCID 178480956, compoundYield 81.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.89 g, 4.28 mmol, 1 equiv), tert-butyl N-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (1.64 g, 5.14 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.271 g, 0.257 mmol, 0.06 equiv), and sodium carbonate monohydrate (1.28 g, 10.3 mmol, 2.4 equiv) in water (13 mL) and DME (18 mL) was heated at 85° C. for 14 h. The mixture was allowed to cool to ambient temperature. Saturated aqueous sodium bicarbonate solution (15 mL) was added and the aqueous portion was extracted with EtOAc (30 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford a pale yellow solid. Purification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH) afforded cis-tert-butyl N-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)carbamate as a white solid (1.76 g, 3.47 mmol):

Workup

  1. temperatureto cool to ambient temperature
  2. extractionthe aqueous portion was extracted with EtOAc (30 mL)
  3. extractionThe organic extract
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a pale yellow solid
  8. customPurification by column chromatography on silica gel (elution with 2 L of 95:4:1 CH2Cl2:Et3N:MeOH)

Sources & evidence

ORD record
ord-5ae7815e34604b1793da03251459dba2
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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