Cesium carbonate → tert-butyl 3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinecarboxylate

HRID 897578Notes

Reaction equation

HRID 897578 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[NH:16][N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1C=CC(S(O[CH:35]2[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([CH:39]3[CH2:35][CH2:36][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:38]3)[N:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([O:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:9][CH:10]=3)[C:22]=12

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 13591085tert-Butyl 3-(tosyloxy)pyrrolidine-1-carboxylateHCID 178508717HCID 178508717, compound

Product 1

HCID 22347007tert-butyl 3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinecarboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-Phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.5 g, 1.648 mmol), tert-butyl 3-{[(4-methylphenyl)sulfonyl]oxy}-1-pyrrolidinecarboxylate (1.12 g, 3.30 mmol) and cesium carbonate (1.07 g, 3.30 mmol) in N,N-dimethyl formamide (12 mL) was heated at 75° C. overnight. The reaction mixture was poured on to ice-water (100 mL). The aqueous layer was extracted with ethyl acetate. 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 ethyl acetate as mobile phase to give tert-butyl 3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinecarboxylate (0.20 g, 28%). 1H NMR (DMSO-d6) δ 1.38 (m, 9H), 2.37 (m 2H), 3.32 (s, 3H), 3.44 (m, 1H), 3.59 (m, 1H), 3.65 (m, 1H), 3.75 (m, 1H), 5.44 (m, 1H), 7.16 (m, 5H), 7.43 (m, 2H), 7.65 (m, 2H), 8.26 (s, 1H).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate
  2. washThe combined organic layer was washed with water
  3. dry with materialbrine, dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-84467f04c0854f11969f74430550fd99
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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