Hydrochloric Acid → (6-(4-methylthiazol-2-ylamino)-5-(phenylthio)Pyridin-3-yl)(tetrahydro-2H-pyran-4-yl)methanol hydrochloride

HRID 911814Notes

Reaction equation

HRID 911814 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.C[Li].C([Li])CCC.[O:29]1[CH2:34][CH2:33][CH:32]([CH:35]=[O:36])[CH2:31][CH2:30]1.[NH4+].[Cl-:38].Cl>C1COCC1>[ClH:38].[CH3:14][C:12]1[N:13]=[C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2]([CH:35]([CH:32]3[CH2:33][CH2:34][O:29][CH2:30][CH2:31]3)[OH:36])=[CH:3][C:4]=2[S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[S:10][CH:11]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 247646135-bromo-N-(4-methylthiazol-2-yl)-3-(phenylthio)pyridin-2-amineHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 86631490(6-(4-methylthiazol-2-ylamino)-5-(phenylthio)Pyridin-3-yl)(tetrahydro-2H-pyran-4-yl)methanol hydrochlorideYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A 10 mL round-bottomed flask was charged with 5-bromo-N-(4-methylthiazol-2-yl)-3-(phenylthio)pyridin-2-amine (250 mg, 0.661 mmol), THF (6 mL) and cooled to −78° C. and methyllithium (0.496 mL, 0.793 mmol) was added. The reaction was stirred for 5 minutes and butyllithium (0.317 mL, 0.793 mmol) was added. The reaction was stirred for 10 minutes and tetrahydro-2H-pyran-4-carbaldehyde (151 mg, 1.32 mmol) was added. The reaction was warmed to ambient temperature and poured into saturated aqueous NH4Cl and extracted with EtOAc (2×20 mL). The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (50% EtOAc in hexanes) to afford the title compound (217 mg, 73.0% yield) after HCl salt formation.

Workup

  1. stirringThe reaction was stirred for 10 minutes
  2. temperatureThe reaction was warmed to ambient temperature
  3. extractionextracted with EtOAc (2×20 mL)
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7c53924689074edba1d8ee1fc0777b64
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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