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4-Amino-1-Boc-piperidine → 1,1-Dimethylethyl 4-[[4-amino-5-(2,3-difluoro-6-methoxybenzoyl)-2-pyrimidinyl]amino]-1-piperidinecarboxylate

HRID 1435248
Notes
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Reaction equation

HRID 1435248 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=2[F:19])=[O:9])=[CH:6][N:5]=[C:4](S(CC)=O)[N:3]=1.[NH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1>CN1CCCC1=O.O>[C:34]([O:33][C:31]([N:28]1[CH2:29][CH2:30][CH:25]([NH:24][C:4]2[N:3]=[C:2]([NH2:1])[C:7]([C:8](=[O:9])[C:10]3[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]([F:18])[C:11]=3[F:19])=[CH:6][N:5]=2)[CH2:26][CH2:27]1)=[O:32])([CH3:37])([CH3:35])[CH3:36]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 12682914-Amino-1-Boc-piperidineHCID 21070554(4-Amino-2-(ethylsulfinyl)pyrimidin-5-yl)(2,3-difluoro-6-methoxyphenyl)methanone

Product 1

HCID 587775881,1-Dimethylethyl 4-[[4-amino-5-(2,3-difluoro-6-methoxybenzoyl)-2-pyrimidinyl]amino]-1-piperidinecarboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent
HCID 13387
N-methyl-2-pyrrolidone
Solvent

Procedure

A solution of (4-amino-2-ethanesulfinyl-pyrimidin-5-yl)-(2,3-difluoro-6-methoxy-phenyl)-methanone (7.7 g, 23 mmol, Example 165) and 4-amino-1N-Boc-piperidine (6.8 g, 34 mmol, Astatech) in 30 mL of 1-methyl-2-pyrrolidinone was heated at 70° C. for 30 minutes. The reaction mixture was diluted with water and extracted with ethyl acetate. The dried (Na2SO4) organic solution was evaporated and the residue was chromatographed on silica gel. Elution with 3:2 ethyl acetate/hexane provided 80% yield of 4-[4-amino-5-(2,3-difluoro-6-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid tert-butyl ester as a colorless solid, mp 114 dec., identical to material prepared in Example 106. Mass Spectrum (LR-ES) M+: 463.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe dried (Na2SO4) organic solution
  3. customwas evaporated
  4. customthe residue was chromatographed on silica gel
  5. washElution with 3:2 ethyl acetate/hexane

Sources & evidence

ORD record
ord-21842b7281274579804a3a0ef377cb77
Source dataset
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07615634B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes