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 2233118Notes

Reaction equation

HRID 2233118 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH2:16]OC)=[N:14][CH:13]=[CH:12][N:11]3[C:19]=2[C:20]2[CH:25]=[CH:24][N:23]=[C:22](S(C)(=O)=O)[N:21]=2)=[CH:4][CH:3]=1.[NH2:30][CH2:31][C:32]([CH3:36])([CH3:35])[CH2:33][OH:34]>C(#N)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[N:14][CH:13]=[CH:12][N:11]3[C:19]=2[C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:30][CH2:31][C:32]([CH3:36])([CH3:35])[CH2:33][OH:34])[N:21]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 1173261-Propanol, 3-amino-2,2-dimethyl-HCID 588695492-(4-Fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methoxymethylimidazo[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 1.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

In a round bottom flask charged with 2-(4-fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methoxymethylimidazo[1,2-a]pyrazine (˜2-3% impurity within 3.05 g, 7.95 mmol of 2-(4-fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazine) was dissolved in ACN (70 mL) to which was added 3-amino-2,2-dimethyl-propan-1-ol (Lancaster, 4.1 g, 96.8 mmol) at ambient temperature followed by heating to about 80° C. for about 3 h. After this time the reaction was cooled to ambient temperature and purified in 200-300 mg batches using RP-HPLC (Table 1, Method i). The pure fractions were combined and concentrated to remove the organic solvent. The resulting precipitate was filtered from the aqueous layer and dried in a vacuum overnight to give the title compound as a white solid (0.054 g, 1.5% yield). LC/MS (Table 1, Method b) Rt=1.77 min; MS m/z: 414.0 (M+H)+.

Workup

  1. temperatureAfter this time the reaction was cooled to ambient temperature
  2. custompurified in 200-300 mg batches
  3. concentrationconcentrated
  4. customto remove the organic solvent
  5. filtrationThe resulting precipitate was filtered from the aqueous layer
  6. customdried in a vacuum overnight

Sources & evidence

ORD record
ord-cba338b3081f463393000c6cd173db2c
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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