1-Propanol, 3-amino-2,2-dimethyl- → 3-{4-[2-(2,4-Difluorophenyl)-8-methylimidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-ylamino}-2,2-dimethylpropan-1-ol

HRID 2233110Notes

Reaction equation

HRID 2233110 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[C:16]([CH3:17])=[N:15][CH:14]=[CH:13][N:12]2[C:18]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=1.[NH2:29][CH2:30][C:31]([CH3:35])([CH3:34])[CH2:32][OH:33]>C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[C:16]([CH3:17])=[N:15][CH:14]=[CH:13][N:12]2[C:18]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([NH:29][CH2:30][C:31]([CH3:35])([CH3:34])[CH2:32][OH:33])[N:20]=1

Participants

4

Reactant 2

HCID 1173261-Propanol, 3-amino-2,2-dimethyl-2×HCID 574387742-(2,4-Difluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazine

Product 1

HCID 160504503-{4-[2-(2,4-Difluorophenyl)-8-methylimidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-ylamino}-2,2-dimethylpropan-1-olYield 59.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(2,4-difluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methyl-imidazo[1,2-a]pyrazine (1.4 g, 3.5 mmol) in ACN (30 mL) was added 3-amino-2,2-dimethyl-propan-1-ol (Lancaster, 0.79 g, 7.7 mmol). The mixture was heated to about 80° C. After about 16 h, the mixture was treated with additional 3-amino-2,2-dimethyl-propan-1-ol (Lancaster, 0.20 g, 1.9 mmol) and heated at about 80° C. for about another 4 h. The mixture was filtered through a pad of silica gel and eluted with EtOAc. The solution was evaporated, triturated with ether, and then filtered. The solid was dissolved in hot methanol (˜10 mL). The solution was cooled and the solvent evaporated. The resulting solid was dried at 100° C. under vacuum to yield the title compound as a white solid (0.88 g, 59%): LC/MS (Table 1, Method g) Rt=2.38 min; MS m/z: 425.2 (M+H)+, mp 173.8-174.5° C.

Workup

  1. temperatureheated at about 80° C. for about another 4 h
  2. filtrationThe mixture was filtered through a pad of silica gel
  3. washeluted with EtOAc
  4. customThe solution was evaporated
  5. customtriturated with ether
  6. filtrationfiltered
  7. dissolutionThe solid was dissolved in hot methanol (˜10 mL)
  8. temperatureThe solution was cooled
  9. customthe solvent evaporated
  10. customThe resulting solid was dried at 100° C. under vacuum

Sources & evidence

ORD record
ord-7423c8573e034e4fa5c4cbf88487ce33
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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