4-Piperidinol, 1-methyl- → HCID 59381904, compound

HRID 2355093Notes

Reaction equation

HRID 2355093 reaction equation
CC(C)([O-])C.[K+].[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1.F[C:16]1[CH:47]=[CH:46][C:45]([C:48]([F:51])([F:50])[F:49])=[CH:44][C:17]=1[C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([C:28]([NH:30][C:31]2[CH:32]=[N:33][C:34]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[N:35][CH:36]=2)=[O:29])[CH:22]=1)=[O:19]>C1COCC1.C(Cl)Cl>[CH3:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:18]([C:17]2[CH:44]=[C:45]([C:48]([F:51])([F:49])[F:50])[CH:46]=[CH:47][C:16]=2[O:14][CH:11]2[CH2:12][CH2:13][N:8]([CH3:7])[CH2:9][CH2:10]2)=[O:19])=[CH:22][C:23]=1[C:28]([NH:30][C:31]1[CH:36]=[N:35][C:34]([NH:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[N:33][CH:32]=1)=[O:29]

Participants

6

Reactant 3

HCID 660484-Piperidinol, 1-methyl-HCID 16116973HCID 16116973, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 59381904HCID 59381904, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of potassium t-butoxide (17 mg, 0.151 mmol) in THF (2 mL) was added 1-methylpiperidin-4-ol (15 mg, 0.130 mmol). The mixture was allowed to stir at rt for 15 min, at which time 2-fluoro-N-(4-methyl-3-(((2-(phenylamino)-5-pyrimidinyl)amino)carbonyl)phenyl)-5-(trifluoromethyl)benzamide 40 (55 mg, 0.108 mmol) was added. The reaction mixture was stirred at room temperature for 24 h, at which time the LCMS showed complete conversion. The reaction mixture was diluted with CH2Cl2, washed with water (3×20 mL), dried over Na2SO4 and concentrated. The crude residue was taken up in MeOH/DMSO and purified on the Shimadzu reversed phase HPLC with a 15-85% gradient. Pure fractions were combined, basified with saturated sodium bicarbonate and extracted with CH2Cl2 (4×20 mL). Combined organic extracts were dried over sodium sulfate and concentrated to afford 2-methyl-5-(((2-((1-methyl-4-piperidinyl)oxy)-5-(trifluoromethyl)phenyl)carbonyl)amino)-N-(2-(phenylamino)-5-pyrimidinyl)benzamide 41. MS m/z found 605.3 [MH+]; calc. for C32H31F3N6O3=604.24.

Workup

  1. additionwas added
  2. washwashed with water (3×20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified on the Shimadzu
  6. extractionextracted with CH2Cl2 (4×20 mL)
  7. dry with materialCombined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1322e1357d784604b144430903c6fa9f
Source dataset
uspto-grants-2010_07
Patent number
US07754717B2

Reaction notes

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