Trifluoroacetic acid → 1-[1-(3-Azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1499782Notes

Reaction equation

HRID 1499782 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]2[N:15]([CH:19]([C:21]3[C:22]([O:40][CH3:41])=[C:23]([CH:29]4[CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]4)[C:24]([CH3:28])=[C:25]([Cl:27])[CH:26]=3)[CH3:20])[N:16]=[C:17]([Br:18])[C:10]=12>C(Cl)Cl.[OH-].[Na+]>[NH:31]1[CH2:32][CH:29]([C:23]2[C:22]([O:40][CH3:41])=[C:21]([CH:19]([N:15]3[C:11]4=[N:12][CH:13]=[N:14][C:9]([NH2:8])=[C:10]4[C:17]([Br:18])=[N:16]3)[CH3:20])[CH:26]=[C:25]([Cl:27])[C:24]=2[CH3:28])[CH2:30]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86677708tert-Butyl 3-{3-[1-(4-amino-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidine-1-carboxylate

Product 1

HCID 866777091-[1-(3-Azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

Trifluoroacetic acid (1.2 mL, 16 mmol) was added to a solution of tert-butyl 3-{3-[1-(4-amino-3-bromo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}azetidine-1-carboxylate (224 mg, 0.407 mmol) in methylene chloride (2.5 mL) and stirred for 2 h at room temp. The mixture was diluted with dichloromethane and 1 N NaOH was added and stirred rapidly for a few minutes. The layers were separated and the aqueous extracted with dichloromethane. The combined organics were dried (MgSO4), filtered, and concentrated. Drying in vacuo gave 163 mg (91%) of the freebase. LCMS calculated for C18H21BrClN6O (M+H)+: m/z=451.1; Found: 451.0.

Workup

  1. additionwas added
  2. stirringstirred rapidly for a few minutes
  3. customThe layers were separated
  4. extractionthe aqueous extracted with dichloromethane
  5. dry with materialThe combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customDrying in vacuo
  9. customgave 163 mg (91%) of the freebase

Sources & evidence

ORD record
ord-9a8362cbfe9347f9b1b08adbb0236951
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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