1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(1-(4-Cyclobutyl-5-(5-ethyl-1H-pyrazol-3-yl)-2-methylbenzoyl)piperidin-4-yl)benzonitrile

HRID 541453Notes

Reaction equation

HRID 541453 reaction equation
[CH:1]1([C:5]2[C:13]([C:14]3[CH:18]=[C:17]([CH2:19][CH3:20])[NH:16][N:15]=3)=[CH:12][C:8]([C:9](O)=[O:10])=[C:7]([CH3:21])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[NH:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1.CCN=C=NCCCN(C)C>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[CH:1]1([C:5]2[C:13]([C:14]3[CH:18]=[C:17]([CH2:19][CH3:20])[NH:16][N:15]=3)=[CH:12][C:8]([C:9]([N:23]3[CH2:28][CH2:27][CH:26]([C:29]4[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=4)[CH2:25][CH2:24]3)=[O:10])=[C:7]([CH3:21])[CH:6]=2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 193916184-(Piperidin-4-yl)benzonitrile--hydrogen chloride (1/1)HCID 682887464-cyclobutyl-5-(5-ethyl-1H-pyrazol-3-yl)-2-methylbenzoic acid2×

Product 1

HCID 682891044-(1-(4-Cyclobutyl-5-(5-ethyl-1H-pyrazol-3-yl)-2-methylbenzoyl)piperidin-4-yl)benzonitrileYield 72%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of 4-cyclobutyl-5-(5-ethyl-1H-pyrazol-3-yl)-2-methylbenzoic acid (compound 445.3, 130 mg, 0.460 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL) were added 4-(Piperidin-4-yl)benzonitrile hydrochloride (1.5, 102 mg, 0.460 mmol, 1.00 equiv), EDCI (176 mg, 0.920 mmol, 2.00 equiv), and 4-dimethylaminopyridine (112 mg, 0.920 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at 30° C., and then diluted with 40 mL of ethyl acetate. The mixture was washed with 3×40 mL of brine, dried (Na2SO4), and concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (59.0% CH3CN up to 73.0% in 6 min, up to 100.0% in 7 min, down to 59.0% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 150 mg (72%) of the title compound as a white solid. m/z (ES+) 453 (M+H)+.

Workup

  1. washThe mixture was washed with 3×40 mL of brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  5. waitmobile phase, water with 0.05% TFA and CH3CN (59.0% CH3CN up to 73.0% in 6 min
  6. waitup to 100.0% in 7 min
  7. waitdown to 59.0% in 1 min)
  8. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-e2237ae0cbed4c1f98c00f2b60bdcf14
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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