p-Toluenesulfonic acid → HCID 178458660, compound

HRID 1641385Notes

Reaction equation

HRID 1641385 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][O:8][C:9]2[N:14]=[C:13]([NH:15][C@H:16]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=3)[CH3:17])[N:12]=[C:11]([NH:25][C:26]3[CH:30]=[C:29]([O:31][CH:32]([CH3:34])[CH3:33])[NH:28][N:27]=3)[C:10]=2[F:35])[CH2:4][O:3]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O>[F:35][C:10]1[C:9]([O:8][CH2:7][C@@H:5]([OH:6])[CH2:4][OH:3])=[N:14][C:13]([NH:15][C@H:16]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=2)[CH3:17])=[N:12][C:11]=1[NH:25][C:26]1[CH:30]=[C:29]([O:31][CH:32]([CH3:34])[CH3:33])[NH:28][N:27]=1

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 178458659HCID 178458659, compound

Product 1

HCID 178458660HCID 178458660, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 887MethanolSolvent

Procedure

To a solution of 6-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}-5-fluoro-N2-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (Example 25; 0.21 g, 0.415 mmol) in methanol (5 ml) was added a few drops of water and then p-toluenesulfonic acid (0.119 g, 0.623 mmol). The mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was subjected to silica gel chromatographic purification (by ISCO Combiflash with gradient EtOAc/hexanes) to afford the desired product as a white solid (0.075 g, yield 40%). LC-MS, 466 (M+1); 1H NMR δ 9.85 (br s, 1H), 8.30 (s, 1H), 7.60 (m, 1H), 7.30 (m, 1H), 5.25 (s, 1H), 4.80-4.90 (m, 2H), 4.60 (m, 2H), 4.0 (br s, 2H), 3.55 (m, 1H), 1.35 (d, 3H), 1.15 (d, 6H).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was subjected to silica gel chromatographic purification (by ISCO Combiflash with gradient EtOAc/hexanes)

Sources & evidence

ORD record
ord-8963b0e2900c491d852c9da6673b5c4b
Source dataset
uspto-grants-2012_02
Patent number
US08114989B2

Reaction notes

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