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

HRID 2233105Notes

Reaction equation

HRID 2233105 reaction equation
[CH:1]1([CH2:4][C:5]2[C:6]3[N:7]([C:11]([C:21]4[CH:26]=[CH:25][N:24]=[C:23](S(C)(=O)=O)[N:22]=4)=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=4)[N:13]=3)[CH:8]=[CH:9][N:10]=2)[CH2:3][CH2:2]1.[NH2:31][CH2:32][C:33]([CH3:37])([CH3:36])[CH2:34][OH:35]>C(#N)C>[CH:1]1([CH2:4][C:5]2[C:6]3[N:7]([C:11]([C:21]4[CH:26]=[CH:25][N:24]=[C:23]([NH:31][CH2:32][C:33]([CH3:37])([CH3:36])[CH2:34][OH:35])[N:22]=4)=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=4)[N:13]=3)[CH:8]=[CH:9][N:10]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 1173261-Propanol, 3-amino-2,2-dimethyl-HCID 588695518-Cyclopropylmethyl-2-(4-fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)imidazo[1,2-a]pyrazine

Product 1

HCID 160504493-{4-[8-Cyclopropylmethyl-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-yl]pyrimidin-2-ylamino}-2,2-dimethylpropan-1-olYield 57.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 8-cyclopropylmethyl-2-(4-fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)imidazo[1,2-a]pyrazine (3.00 g, 7.08 mmol) and 3-amino-2,2-dimethylpropan-1-ol (TCI-US, 3.65 g, 35.4 mmol) in ACN (100 mL) was heated at about 85° C. for about 2 d. After cooling to ambient temperature, a precipitate formed, which was filtered off, washed with ACN, dried in vacuo and purified by silica gel chromatography with heptane/EtOAc (gradient 50-100% EtOAc, then isocratic 100% EtOAc). After concentration, the residue was three times re-dissolved in DCM and re-concentrated, resulting in a colorless foam, which was dried in a vacuum oven for about 16 h at about 55° C. and about 21 Torr to give 1.809 g (56%) of the title compound as a colorless solid: LC/MS (Table 1, Method g) Rt=3.01 min; MS m/z: 447.2 (M+H)+.

Workup

  1. customa precipitate formed
  2. filtrationwhich was filtered off
  3. washwashed with ACN
  4. customdried in vacuo
  5. custompurified by silica gel chromatography with heptane/EtOAc (gradient 50-100% EtOAc
  6. concentrationAfter concentration
  7. dissolutionre-dissolved in DCM
  8. concentrationre-concentrated
  9. customresulting in a colorless foam, which
  10. customwas dried in a vacuum oven for about 16 h at about 55° C.

Sources & evidence

ORD record
ord-1805ea87cdc04c5480a83f6b2e77cd62
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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