Dimethylformamide → N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]-methyl]thio]-2-thiazolyl]-1-(1-methylethyl)-4-piperidinecarboxamide

HRID 1861833Notes

Reaction equation

HRID 1861833 reaction equation
Cl.CN(C)CCCN=C=NCC.[NH2:13][C:14]1[S:15][C:16]([S:19][CH2:20][C:21]2[O:22][C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:24][N:25]=2)=[CH:17][N:18]=1.[CH3:30][CH:31]([N:33]1[CH2:38][CH2:37][CH:36]([C:39](O)=[O:40])[CH2:35][CH2:34]1)[CH3:32].CN(C)C=O>CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[CH3:27][C:26]([C:23]1[O:22][C:21]([CH2:20][S:19][C:16]2[S:15][C:14]([NH:13][C:39]([CH:36]3[CH2:37][CH2:38][N:33]([CH:31]([CH3:32])[CH3:30])[CH2:34][CH2:35]3)=[O:40])=[N:18][CH:17]=2)=[N:25][CH:24]=1)([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 64841871-Isopropylpiperidine-4-Carboxylic AcidHCID 110654845-(((5-(tert-Butyl)oxazol-2-yl)methyl)thio)thiazol-2-amine

Product 1

HCID 10224089N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]-methyl]thio]-2-thiazolyl]-1-(1-methylethyl)-4-piperidinecarboxamideYield 85%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.0 g, 5.2 mmol, 2 eq) was added to a mixture of 2-amino-5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]thiazole (0.7 g, 2.6 mmol, 1 eq), 1-(1-methylethyl)-4-piperidine carboxylic acid (0.78 g, 3.9 mmol, 1.5 eq), 4-(dimethylamino)pyridine (0.16 g, 1.3 mmol, 0.5 eq), N,N-dimethylformamide (2.6 mL) and CH2Cl2 (7.8 mL). The reaction mixture was stirred at rt for 1 h, diluted with 30 mL of water and extracted with ethyl acetate (2×70 mL). The organic extracts were dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography on silica gel eluting with a gradient of 5-10% triethylamine in ethyl acetate. The material was recrystallized from ethanol and water to provide 0.93 g (85%) of N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]- 1-(1-methylethyl)-4-piperidinecarboxamide as a yellowish solid. MS: 423 [M+H]+; HPLC: 100% at 3.15 min (YMC S5 ODS column 4.6×50 mm, 10-90% aqueous methanol over 4 minutes containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm).

Workup

  1. extractionextracted with ethyl acetate (2×70 mL)
  2. dry with materialThe organic extracts were dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography on silica gel eluting with a gradient of 5-10% triethylamine in ethyl acetate
  5. customThe material was recrystallized from ethanol and water

Sources & evidence

ORD record
ord-186a93fcc5d343e794f04395ea1c2a86
Source dataset
uspto-grants-2003_03
Patent number
US06534531B2

Reaction notes

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