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

HRID 2233099Notes

Reaction equation

HRID 2233099 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20](S(C)(=O)=O)[N:19]=2)=[CH:4][CH:3]=1.[NH2:28][CH2:29][C:30]([CH3:34])([CH3:33])[CH2:31][OH:32]>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:17]=2[C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH:28][CH2:29][C:30]([CH3:34])([CH3:33])[CH2:31][OH:32])[N:19]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 1173261-Propanol, 3-amino-2,2-dimethyl-HCID 588695482-(4-Fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazine

Product 1

HCID 159814043-{4-[2-(4-Fluorophenyl)-8-methylimidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-ylamino}-2,2-dimethylpropan-1-olYield 86%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-(4-fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazine (1.50 g, 391 mmol) in ACN (30 mL) was added 3-amino-2,2-dimethyl-1-propanol (Lancaster, 2.0 g, 20 mmol). The reaction mixture was heated to about 80° C. After about 1.5 h, the reaction was cooled to ambient temperature and concentrated under reduced pressure. The resulting crude material was purified by silica gel chromatography with DCM/MeOH/NH4OH (step-wise gradient, 990:9:1 then 980:18:2) to give an oil after concentration. The oil was dissolved in a minimum amount of DCM and heptane was added until a white precipitate formed. The suspension was concentrated under reduced pressure. The resulting solid was triturated with heptane and filtered to give the title compound (1.36 g, 86%): LC/MS (Table 1, Method g) Rt=2.41 min; MS m/z: 407.2 (M+H)+.

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting crude material was purified by silica gel chromatography with DCM/MeOH/NH4OH (step-wise gradient, 990:9:1
  4. custom980:18:2) to give an oil
  5. concentrationafter concentration
  6. dissolutionThe oil was dissolved in a minimum amount of DCM and heptane
  7. additionwas added until a white precipitate
  8. customformed
  9. concentrationThe suspension was concentrated under reduced pressure
  10. customThe resulting solid was triturated with heptane
  11. filtrationfiltered

Sources & evidence

ORD record
ord-9c1aee2d7ef64964891294ffd6b1165e
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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