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

HRID 1361762Notes

Reaction equation

HRID 1361762 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-fb0e9490b3934fdb8cb0e1dd93754bb4
Source dataset
uspto-grants-2011_02
Patent number
US07880013B2

Reaction notes

Loading…