Dichloromethane → HCID 17987974, compound

HRID 1982931Notes

Reaction equation

HRID 1982931 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]3[N:26]([C:34]4[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=4)[N:27]=[C:28]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:29]=3)=[O:23])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(Cl)[Cl:42]>O1CCOCC1>[ClH:42].[C:30]([C:28]1[CH:29]=[C:25]([NH:24][C:22]([NH:21][C:18]2[CH:17]=[CH:16][C:15]([CH2:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:20][CH:19]=2)=[O:23])[N:26]([C:34]2[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=2)[N:27]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 57712321HCID 57712321, compound

Product 1

HCID 17987974HCID 17987974, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-(carboxy-benzyl)-piperidine-1-carboxylic acid tert-butyl ester (1.595 g, 5.0 mmol) in THF (25 mL) at room temp is added TEA (0.77 mL, 5.5 mmol) followed by DPPA (1.18 mL, 5.5 mmol). The mixture is refluxed for 1 hour and 3-amino-4-tert-butyl-2-tolylpyrazole (1.26 g, 5.5 mmol) is added and the reaction is refluxed overnight. The reaction is cooled and partitioned between ether-aqueous NH4Cl, and the organic layer is washed with brine, then dried over MgSO4, filtered and evaporated. The residue is chromatographed on silica gel using ethyl acetate/heptane (3:7) chloride to yield 1.22 grams of 4-{4-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-benzyl}-piperidine-1-carboxylic acid tert-butyl ester. 4-{4-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureido]-benzyl}-piperidine-1-carboxylic acid tert-butyl ester (3.24 g, 5.94 mmol) is dissolved in methylene chloride (20 mL) under nitrogen at 0° C. and 4N HCL in dioxane (3 ml) is added. After 10 minutes the cooling bath is removed and the reaction is stirred for 3 hours at room temp. The solution is concentrated to a foam which solidified after stirring in ether for a few hours. The solid is filtered and air dried to give 2.8 grams of 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3(4-piperidin-4-ylmethyl-phenyl)-urea hydrochloride. Intermediate 4, LCMS M+1 446, RT=2.82 minutes.

Workup

  1. customAfter 10 minutes the cooling bath is removed
  2. concentrationThe solution is concentrated to a foam which
  3. stirringafter stirring in ether for a few hours
  4. filtrationThe solid is filtered
  5. customair dried

Sources & evidence

ORD record
ord-a08ab7dfa18f402cbceb8bfec66dcdff
Source dataset
uspto-grants-2009_06
Patent number
US07541368B2

Reaction notes

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