2,2-Dimethylpentanoic acid → HCID 68539322, compound

HRID 1993700Notes

Reaction equation

HRID 1993700 reaction equation
[CH3:1][C:2]1([C:5]2[CH:6]=[C:7]([NH:17][C:18]([NH:20][C:21]3[CH:22]=[N:23][C:24]([N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[CH:25][CH:26]=3)=[O:19])[N:8]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)[N:9]=2)[CH2:4][CH2:3]1.[CH3:33][C:34]([CH3:41])([CH2:38][CH2:39][CH3:40])[C:35](O)=[O:36].Cl.CN(C)CCCN=C=NCC>CN(C1C=CN=CC=1)C.ClCCl>[CH3:33][C:34]([CH3:41])([CH2:38][CH2:39][CH3:40])[C:35]([N:30]1[CH2:31][CH2:32][N:27]([CH:24]2[NH:23][CH2:22][CH:21]([NH:20][C:18]([NH:17][C:7]3[N:8]([C:10]4[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=4)[N:9]=[C:5]([C:2]4([CH3:1])[CH2:3][CH2:4]4)[CH:6]=3)=[O:19])[CH2:26][CH2:25]2)[CH2:28][CH2:29]1)=[O:36]

Participants

6

Reactant 3

HCID 144552,2-Dimethylpentanoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68540130HCID 68540130, compound

Product 1

HCID 68539322HCID 68539322, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Treat a solution or slurry of the 1-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-(6-piperazin-1-yl-pyridin-3-yl)-urea (Preparation 5, 1 equiv., 0.1510 g), 2,2-dimethyl pentanoic acid (1.15 equiv., 0.0521 g) and catalytic DMAP (ca. 0.1 equiv., 0.049 g) in dichloromethane (ca. 0.1 M, 5 mL) with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC1.15 equiv., 0.0767 g). Agitate the resulting mixture at ambient temperature for 48 hours then wash with saturated aq. sodium bicarbonate solution. Dry the organic layer over sodium sulfate and concentrate under reduced pressure. Purification A: Purify on silica gel using a gradient 2 M ammonia-methanol in dichloromethane, a gradient of ethyl acetate in dichloromethane or hexanes. Purification B: Purify by reverse phase on an Xterra 30×75 mm 5 micron MS C18 column using a gradient of aqueous 10 mM ammonium bicarbonate in acetonitrile affords the title compound. LCMS(ES+): m/z=544. [M+H].

Workup

  1. washthen wash with saturated aq. sodium bicarbonate solution
  2. dry with materialDry the organic layer over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customPurification A:
  5. customPurify on silica gel using a gradient 2 M ammonia-methanol in dichloromethane
  6. customPurification B
  7. customPurify by reverse phase on an Xterra 30×75 mm 5 micron MS C18 column

Sources & evidence

ORD record
ord-43814e264e5c4516969340a32611283e
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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