Diisopropylethylamine → HCID 59632892, compound

HRID 2369080Notes

Reaction equation

HRID 2369080 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28](Cl)=[O:29])=[N:9]1.C(N(CC)C(C)C)(C)C.[NH:40]1[CH2:49][CH2:48][CH:43]([C:44]([O:46][CH3:47])=[O:45])[CH2:42][CH2:41]1>CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=3)=[CH:16][CH:17]=2)=[CH:11][C:10]([C:28]([N:40]2[CH2:49][CH2:48][CH:43]([C:44]([O:46][CH3:47])=[O:45])[CH2:42][CH2:41]2)=[O:29])=[N:9]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 424914Methyl isonipecotateHCID 59632099HCID 59632099, compound

Product 1

HCID 59632892HCID 59632892, compoundYield 8.2%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To a solution of 1-(2-chlorophenyl)-5-(5-(3-(methylsulfonyl)phenyl)thiophen-2-yl)-1H-pyrazole-3-carbonyl chloride (0.23 mmol crude from previous step) in CDCl3 (12 ml) was added N,N-diisopropylethylamine (150 μL, 0.86 mmol) and a small amount of DMAP. The resulting mixture was treated with methyl isonipecotate (62 μL, 0.46 mmol). After stirring for 3 hours at ambient temperature the reaction was quenched by dilution with H2O, and dilution with CH2Cl2. The layers were separated and the basic aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure to afford crude product. This material was purified by flash column chromatography eluting with a gradient from 0% to 16% MeCN in CH2Cl2 to afford methyl 1-{[1-(2-chlorophenyl)-5-{5-[3-(methylsulfonyl)phenyl]-2-thienyl}-1H-pyrazol-3-yl]carbonyl}piperidine-4-carboxylate (11 mg, 8% yield) as a white powder. MS(ES): 584 [M+H]+.

Workup

  1. customwas quenched by dilution with H2O, and dilution with CH2Cl2
  2. customThe layers were separated
  3. extractionthe basic aqueous layer was extracted with CH2Cl2
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude product
  8. customThis material was purified by flash column chromatography
  9. washeluting with a gradient from 0% to 16% MeCN in CH2Cl2

Sources & evidence

ORD record
ord-6aff990a706c43fe96e6353beeb1f485
Source dataset
uspto-grants-2014_04
Patent number
US08703805B2

Reaction notes

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