Triethylamine → {4-[3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1809707Notes

Reaction equation

HRID 1809707 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][C:13](Cl)=[N:14][CH:15]=3)[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.Cl[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31].[C:34]([NH:41][C@H:42]1[CH2:47][CH2:46][C@H:45]([NH2:48])[CH2:44][CH2:43]1)([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>CN(C=O)C.O>[C:37]([O:36][C:34](=[O:35])[NH:41][CH:42]1[CH2:43][CH2:44][CH:45]([NH:48][C:13]2[N:12]=[C:11]3[N:10]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:9]=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=4)[C:16]3=[CH:15][N:14]=2)[CH2:46][CH2:47]1)([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178419079HCID 178419079, compoundHCID 178478326HCID 178478326, compound

Product 1

HCID 68108922{4-[3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(3-bromo-phenyl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidine (from Example 38 supra) (3.0 g, 9.7 mmol), Et3N (5.4 mL, 38.8 mmol) in DMF (50 mL), (2-(chloromethoxy)-ethyl)trimethylsilane (SEM-Cl, 2.0 mL, 11.6 mmol) was added in one portion. The resultant mixture was stirred for 30 minutes at room temperature. To this solution, N-Boc-trans-1,4-cyclohexanediamine (2.48 g, 11.6 mmol) was added. The resulting mixture was stirred for one hour at room temperature. The reaction was then poured into water (200 mL) and extracted with EtOAc (3×200 mL). The EtOAc extract was dried over Na2SO4, filtered and concentrated. The crude product was purified by chromatography (silica gel, 200-300 mesh, EtOAc) to give {4-[3-(3-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-6-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester as yellow oil. (Yield 2.2 g, 37.3%).

Workup

  1. extractionextracted with EtOAc (3×200 mL)
  2. extractionThe EtOAc extract
  3. dry with materialwas dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by chromatography (silica gel, 200-300 mesh, EtOAc)

Sources & evidence

ORD record
ord-92e877238aa44ff8af98d3ec62cd6413
Source dataset
uspto-grants-2013_01
Patent number
US08362023B2

Reaction notes

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