Triethylamine → 1-(tert-Butoxycarbonyl)-N-[4-(2-furyl)-5-morpholinothiazol-2-yl]piperidine-4-carboxamide

HRID 1967739Notes

Reaction equation

HRID 1967739 reaction equation
[NH2:1][C:2]1[S:3][C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:5]([C:7]2[O:8][CH:9]=[CH:10][CH:11]=2)[N:6]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31](O)=[O:32])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C.O>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]([NH:1][C:2]2[S:3][C:4]([N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)=[C:5]([C:7]3[O:8][CH:9]=[CH:10][CH:11]=3)[N:6]=2)=[O:32])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 2724699PyBOPHCID 231441582-Amino-4-(2-furyl)-5-morpholinothiazole

Product 1

HCID 231441631-(tert-Butoxycarbonyl)-N-[4-(2-furyl)-5-morpholinothiazol-2-yl]piperidine-4-carboxamideYield 68.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Amino-4-(2-furyl)-5-morpholinothiazole (3.58 g, 14.3 mmol) obtained in Step 1 of Example 29, 1-(tert-butoxycarbonyl)-4-piperidinecarboxylic acid (3.27 g, 14.3 mmol) and PyBOP (8.16 g, 15.7 mmol) were dissolved in DMF (30 mL), and triethylamine (4.37 mL, 31.4 mmol) was added thereto, followed by stirring overnight at room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed successively with 1 mol/L hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:1) to afford the entitled Compound 42 (4.52 g, 68%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed successively with 1 mol/L hydrochloric acid
  3. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled away under reduced pressure
  5. customThe resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-7f412cda5bbc486a8c7f060b549e7914
Source dataset
uspto-grants-2013_04
Patent number
US08420827B2

Reaction notes

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