Isopropanol → HCID 131732849, compound

HRID 575533Notes

Reaction equation

HRID 575533 reaction equation
CC(O)C.C([Cl:8])(=O)C.[NH2:9][C:10]1[C:15]([CH2:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24](=[O:35])[C@@H:25]([NH:27]C(=O)OC(C)(C)C)[CH3:26])[CH2:20][CH2:19]2)=[C:14]([Cl:36])[N:13]=[C:12]([CH3:37])[N:11]=1>C(OCC)C>[ClH:8].[ClH:36].[NH2:27][C@@H:25]([CH3:26])[C:24]([N:21]1[CH2:22][CH2:23][CH:18]([CH2:17][CH2:16][C:15]2[C:10]([NH2:9])=[N:11][C:12]([CH3:37])=[N:13][C:14]=2[Cl:36])[CH2:19][CH2:20]1)=[O:35]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 6367Acetyl chlorideHCID 118061845HCID 118061845, compound

Product 1

HCID 131732849HCID 131732849, compoundYield 203.7%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Heat IPA (154 mL) to 50° C. and add acetyl chloride (19.3 mL, 271 mmol) slowly due to an exothermic reaction. Stir the reaction at 50° C. for 10 min and then add tert-butyl N-[(1S)-2-[4-[2-(4-amino-6-chloro-2-methyl-pyrimidin-5-yl)ethyl]-1-piperidyl]-1-methyl-2-oxo-ethyl]carbamate (21.0 g, 45.3 mmol). Stir the reaction for 2 h monitoring via LCMS (low pH). Cool the reaction to RT and add diethyl ether (386 mL). Stir the slurry for 15 min. Filter the solids, washing with diethyl ether (2×50 mL) in a brisk manner as the material is hydroscopic. Filter the material and dry via filtration for 1 min, then in a vacuum drying oven at 50° C. overnight to give the title compound as a white powder (18.4 g). LC-ES/MS m/z (35Cl/37Cl) 326.1/328.2 (M+1). Counterion analysis by ion chromatography is consistent with the dihydrochloride salt.

Workup

  1. customslowly due to an exothermic reaction
  2. customthe reaction at 50° C. for 10 min
  3. stirringStir
  4. customthe reaction for 2 h
  5. temperatureCool
  6. customthe reaction to RT
  7. stirringStir the slurry for 15 min
  8. filtrationFilter the solids
  9. washwashing with diethyl ether (2×50 mL) in a brisk manner as the material
  10. filtrationFilter the material
  11. customdry via filtration for 1 min
  12. customin a vacuum drying oven at 50° C. overnight

Sources & evidence

ORD record
ord-449c0f30fcfd415c956057f9259b4e50
Source dataset
uspto-grants-2015_05
Patent number
US09035051B1

Reaction notes

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