Trifluoroacetic acid → 1-[3-(4-Amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)phenyl]ethanone

HRID 238012Notes

Reaction equation

HRID 238012 reaction equation
CO[C:3]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[CH:5][C:4]=1NC(=O)OC(C)(C)C.[CH:26]1([N:31]2[C:35]3=[N:36][CH:37]=[N:38][C:39]([NH2:40])=[C:34]3[C:33](I)=[N:32]2)[CH2:30]CC[CH2:27]1.C([O-])([O-])=O.[Na+].[Na+].[C:48](O)([C:50](F)(F)F)=[O:49].B(Br)(Br)Br>CCO.COCCOC.C(Cl)Cl.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>[NH2:40][C:39]1[N:38]=[CH:37][N:36]=[C:35]2[N:31]([CH:26]([CH3:27])[CH3:30])[N:32]=[C:33]([C:7]3[CH:8]=[C:3]([C:48](=[O:49])[CH3:50])[CH:4]=[CH:5][CH:6]=3)[C:34]=12

Participants

10

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 25134Boron tribromideHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 223468081-cyclopentyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 529458451-[3-(4-Amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)phenyl]ethanone

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (200 mg, 0.76 mmol) in EtOH (3.3 ml) was added to a solution of 1-cyclopentyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (BA80, 100 mg, 0.30 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified using silica gel column chromatography [MeOH—CH2Cl2, 5:95] yielding BA81. BA81 was dissolved in 50:50 CH2Cl2:TFA and stirred for one hour at room temperature. The reaction mixture was concentrated in vacuo and purified using by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA81d. BA81d was dissolved in CH2Cl2 (2 ml) and BBr3 (4 mL, 4 mol) was added slowly with a syringe, while stirring. The reaction was stirred at room temperature for 2 hours then concentrated in vacuo and purified using by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA81dd.

Workup

  1. temperatureAfter cooling
  2. extractionthe reaction was extracted with saturated NaCl and CH2Cl2
  3. concentrationconcentrated in vacuo
  4. custompurified
  5. customyielding BA81
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. custompurified
  8. customto yield BA81d
  9. stirringThe reaction was stirred at room temperature for 2 hours
  10. concentrationthen concentrated in vacuo
  11. custompurified
  12. customto yield BA81dd

Sources & evidence

ORD record
ord-0062667054a6491989a46a21eeea6503
Source dataset
uspto-grants-2014_02
Patent number
US08642604B2

Reaction notes

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