Triethylamine → HCID 49780483, compound

HRID 1923623Notes

Reaction equation

HRID 1923623 reaction equation
[CH2:1]([C:5]1[C:9](/[CH:10]=[CH:11]/[C:12]2[S:13][C:14]([C:18]([OH:20])=O)=[C:15]([CH3:17])[N:16]=2)=[C:8]([CH3:21])[O:7][N:6]=1)[CH2:2][CH2:3][CH3:4].Cl.[F:23][C:24]1([F:28])[CH2:27][NH:26][CH2:25]1.ON1C(=O)CCC1=O.C(N(CC)CC)C>CN(C=O)C.O>[CH2:1]([C:5]1[C:9](/[CH:10]=[CH:11]/[C:12]2[S:13][C:14]([C:18]([N:26]3[CH2:27][C:24]([F:28])([F:23])[CH2:25]3)=[O:20])=[C:15]([CH3:17])[N:16]=2)=[C:8]([CH3:21])[O:7][N:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80170N-HydroxysuccinimideHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 595685392-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid

Product 1

HCID 49780483HCID 49780483, compoundYield 29.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a stirred solution of 2-[(E)-2-(3-butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid (200 mg, 0.65 mmol), 3,3-difluoroazetidine hydrochloride (93 mg, 0.72 mmol) and N-hydroxysuccinimide (86 mg, 0.74 mmol) in DMF (1 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarboiimide (144 mg, 0.75 mmol) and DMF (1 mL) followed by triethylamine (0.29 mL, 2.1 mmol) and DMF (2 mL). The resulting mixture was stirred under argon for 20 h and then water added and the mixture extracted with ethyl acetate. The combined organic extracts were dried, filtered and concentrated. Purification by chromatography (silica, 40% ethyl acetate in heptane) gave the title compound (73 mg, 29%) as pale yellow oil. MS: m/e=382.1 [M+H]+.

Workup

  1. extractionthe mixture extracted with ethyl acetate
  2. customThe combined organic extracts were dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by chromatography (silica, 40% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-e7f7d73889ce472e896bf351eec600f7
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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