[(1s,4s)-4-Aminocyclohexyl]methanol hydrochloride → (4-{4-[4-(3-Methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanol

HRID 1947042Notes

Reaction equation

HRID 1947042 reaction equation
CS([C:4]1[N:9]=[C:8]([N:10]2[C:18]3[C:13](=[C:14]([O:19][CH2:20][CH2:21][CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:15]=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)[CH:7]=[CH:6][N:5]=1)=O.Cl.[NH2:28][CH:29]1[CH2:34][CH2:33][CH:32]([CH2:35][OH:36])[CH2:31][CH2:30]1>CCO>[CH3:26][S:23]([CH2:22][CH2:21][CH2:20][O:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[CH:12]=[CH:11][N:10]2[C:8]1[CH:7]=[CH:6][N:5]=[C:4]([NH:28][CH:29]2[CH2:34][CH2:33][CH:32]([CH2:35][OH:36])[CH2:31][CH2:30]2)[N:9]=1)(=[O:25])=[O:24]

Participants

4

Reactant 2

HCID 24194144[(1s,4s)-4-Aminocyclohexyl]methanol hydrochlorideHCID 580170861-(2-methanesulfinyl-pyrimidin-4-yl)-4-(3-methanesulfonyl-propoxy)-1H-indole

Product 1

HCID 59743554(4-{4-[4-(3-Methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanolYield 49.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-(2-Methanesulfinyl-pyrimidin-4-yl)-4-(3-methanesulfonyl-propoxy)-1H-indole (5.0 g, 13 mmol) and (4-amino-cyclohexyl)-methanol hydrochloride (2.46 g, 19 mmol) were heated at reflux in EtOH (100 mL) under N2 for 16 h. The reaction mixture was then cooled, the suspension filtered, the filtrate volume reduced by half, diluted with EtOAc and washed with water, dried over sodium sulfate, filtered and concentrated until precipitate formed. This suspension was filtered, and the filtrate concentrated again until precipitation, and the suspension filtered, and both precipitates were combined and solvent removed in vacuo to yield (4-{4-[4-(3-methanesulfonyl-propoxy)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanol (Compound 214, 2.93 g), as a light yellow powder.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. filtrationthe suspension filtered
  3. additiondiluted with EtOAc
  4. washwashed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated until precipitate
  8. customformed
  9. filtrationThis suspension was filtered
  10. concentrationthe filtrate concentrated again until precipitation
  11. filtrationthe suspension filtered
  12. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-19a75e557df24e2e9700fd95e96e12f1
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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