Triethylamine → HCID 59506987, compound

HRID 1800689Notes

Reaction equation

HRID 1800689 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[N:9]=[C:10]([N:15]([CH3:36])[C:16]3[CH:17]=[C:18]([NH:22][C:23](=[O:35])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([C:33]#[N:34])([CH3:32])[CH3:31])[CH:25]=4)[CH:19]=[CH:20][CH:21]=3)[N:11]=[CH:12][C:13]=2[N:14]=1)=[O:4].C(N(CC)CC)C.Cl.[F:45][CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C(=O)([O-])O.[Na+]>O1CCCC1>[C:33]([C:30]([C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][CH:27]=1)[C:23]([NH:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([N:15]([C:10]2[N:11]=[CH:12][C:13]3[N:14]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:49]4[CH2:50][CH2:51][CH:46]([F:45])[CH2:47][CH2:48]4)[S:7][C:8]=3[N:9]=2)[CH3:36])[CH:17]=1)=[O:35])([CH3:32])[CH3:31])#[N:34]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27591584-Fluoropiperidine hydrochlorideHCID 59507038HCID 59507038, compound

Product 1

HCID 59506987HCID 59506987, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-{3-[{2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}(methyl)amino]phenyl}-3-(1-cyano-1-methylethyl)benzamide (140 mg, 269 μmol) produced in Example D10 in tetrahydrofuran (4 mL) were added triethylamine (112 μL, 807 μmol) and 4-fluoropiperidine hydrochloride (113 mg, 807 μmol), and the mixture was stirred at 60° C. for 20 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (10 mL), and the mixture was extracted with ethyl acetate (15 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→20/80), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate and hexane to give the title compound (79 mg, 50%) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (15 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=40/60→20/80)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-66f941359ee441468125072d53fcaa5e
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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