Diisopropylethylamine → 2-amino-N-(1-methyl-4-piperidyl)-1,3-thiazole-4-carboxamide

HRID 2234427Notes

Reaction equation

HRID 2234427 reaction equation
Br.[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([OH:10])=O)[N:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:35][CH:36]1[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[O:10])[N:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27375314-Amino-1-methylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 162177172-Amino-4-thiazolecarboxylic acid hydrobromide

Product 1

HCID 627890662-amino-N-(1-methyl-4-piperidyl)-1,3-thiazole-4-carboxamideYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Aminothiazole-4-carboxylate hydrobromide salt (Chempacific; 1.13 g, 5.02 mmol), HATU (2.87 g, 7.53 mmol) and 4-amino-1-methylpiperidine (0.86 g, 7.53 mmol) were stirred in DMF (5 mL) and DIPEA (5.2 mL, 30.12 mmol) added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue taken up in methanol, absorbed onto an SCX column, washed with methanol and eluted with ammonia in methanol. Product containing fractions were combined, evaporated and the residue and further purified by column chromatography (5% 7N NH3 in MeOH/DCM) Product containing fractions were combined and evaporated to give the title compound as a yellow solid (635 mg, 53%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customabsorbed onto an SCX column
  3. washwashed with methanol
  4. washeluted with ammonia in methanol
  5. additionProduct containing fractions
  6. customevaporated
  7. customthe residue and further purified by column chromatography (5% 7N NH3 in MeOH/DCM) Product
  8. additioncontaining fractions
  9. customevaporated

Sources & evidence

ORD record
ord-804b6f9d0a684bb2848bff3904e15ed0
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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