1,2-Dimethoxyethane → tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate

HRID 897584Notes

Reaction equation

HRID 897584 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]1[CH2:12][CH2:11][CH:10]([N:13]2[C:17]3=[N:18][CH:19]=[N:20][C:21]([NH2:22])=[C:16]3[C:15](I)=[N:14]2)[CH2:9][CH2:8]1.[CH3:24][O:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]=1[NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45].C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O>[NH2:22][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:13]([CH:10]3[CH2:11][CH2:12][N:7]([CH2:6][C:2]4[NH:3][CH:4]=[CH:5][N:1]=4)[CH2:8][CH2:9]3)[N:14]=[C:15]([C:30]3[CH:29]=[CH:28][C:27]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[C:26]([O:25][CH3:24])[CH:31]=3)[C:16]=12

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 177502214-(tert-Butoxycarbonylamino)-3-methoxyphenylboronic acid, pinacol esterHCID 223466771-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 22347020tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamateYield 41.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-[1-(1H-2-Imidazolylmethyl)-4-piperidyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (127 mg, 0.299 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (115 mg, 0.329 mmol), palladium tetrakistriphenyphosphine (21 mg, 0.018 mmol) and sodium carbonate (76 mg, 0.718 mmol) were mixed with ethylene glycol dimethyl ether (3 mL) and water (1.5 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5) as mobile phase to give tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (64 mg, 41%). 1H NMR (DMSO-d6) δ 1.48 (m, 9H), 1.87 (m, 2H), 2.23 (m, 4H), 2.94 (m, 2H), 3.56 (s, 2H), 3.88 (s, 3H), 4.66 (m, 1H), 6.92(s, 2H), 7.21 (m, 2H), 7.90 (d, J=8.14, 1H), 8.04 (s, 1H), 8.22 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customOrganic solvent was removed under reduced pressure
  4. extractionthe aqueous layer was extracted with dichloromethane
  5. washThe combined organic layer was washed with water
  6. dry with materialbrine, dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-f61cb500d35948868ff9a8543fe3582f
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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