Water → tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}propanoate

HRID 1499835Notes

Reaction equation

HRID 1499835 reaction equation
Br[C:2]1[C:3]([O:23][CH3:24])=[C:4]([CH:10]([N:12]2[C:16]3=[N:17][CH:18]=[N:19][C:20]([NH2:21])=[C:15]3[C:14]([CH3:22])=[N:13]2)[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:33]1([CH3:39])[CH:38]=CC=C[CH:34]=1.[OH2:40]>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>[NH2:21][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[N:12]([CH:10]([C:4]3[C:3]([O:23][CH3:24])=[C:2]([CH2:7][CH2:2][C:3]([O:23][C:33]([CH3:34])([CH3:38])[CH3:39])=[O:40])[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=3)[CH3:11])[N:13]=[C:14]([CH3:22])[C:15]=12

Participants

6

Reactant 4

HCID 962WaterHCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 866776451-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 86677756tert-Butyl 3-{3-[1-(4-amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}propanoate

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
110 °C

Procedure

To a microwave vial was added 1-[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (Peak 1 from Example 167, step 4 chiral separation, 35 mg, 0.085 mmol), potassium (3-tert-butoxy-3-oxopropyl)trifluoroborane (30.0 mg, 0.13 mmol, from Frontier Scientific, item # P10370), potassium phosphate (54 mg, 0.26 mmol) and tetrakis(triphenylphosphine)palladium(0) (9.8 mg, 0.0085 mmol) and toluene (0.7 mL)/water (0.2 mL). The vial was sealed and degassed with N2 three times. The reaction was heated at 110° C. for 20 h. The crude was filtered and the product (20 mg, 50%) was purified by chromatography eluting with CH2Cl2/MeOH (max. MeOH 6%). LCMS calculated for C23H31ClN5O3 (M+H)+: m/z=460.2; Found: 460.3.

Workup

  1. customThe vial was sealed
  2. customdegassed with N2 three times
  3. filtrationThe crude was filtered
  4. customthe product (20 mg, 50%) was purified by chromatography
  5. washeluting with CH2Cl2/MeOH (max. MeOH 6%)

Sources & evidence

ORD record
ord-3330e5bebe394ac8ac0ecfe4af3f696d
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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