Potassium Carbonate → N-[6-amino-1-cyclobutylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-acetamide

HRID 858071Notes

Reaction equation

HRID 858071 reaction equation
[NH2:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[C:4](=[O:17])[C:3]=1[NH:18][C:19](=[O:39])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][S:28]([C:31]2[C:32]([CH3:38])=[N:33][N:34]([CH3:37])[C:35]=2[Cl:36])(=[O:30])=[O:29])=[CH:23][N:22]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:47][CH:48]1[CH2:51][CH2:50][CH2:49]1>CN(C=O)C>[NH2:1][C:2]1[N:7]([CH2:47][CH:48]2[CH2:51][CH2:50][CH2:49]2)[C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])[C:4](=[O:17])[C:3]=1[NH:18][C:19](=[O:39])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27][S:28]([C:31]2[C:32]([CH3:38])=[N:33][N:34]([CH3:37])[C:35]=2[Cl:36])(=[O:30])=[O:29])=[CH:23][N:22]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 58762839HCID 58762839, compound

Product 1

HCID 69115794N-[6-amino-1-cyclobutylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-acetamideYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A solution of N-[6-amino-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-acetamide in N,N,-dimethylformamide was treated with potassium carbonate (4.0 eq.) and (bromomethyl)cyclobutane (2.0 eq.). The reaction mixture was heated to 40° C. for 16 h. At this time, the N,N,-dimethylformamide was removed in vacuo. The residue was triturated with chloroform and then methanol to remove impurities. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 10/90 methanol/chloroform) afforded N-[6-amino-1-cyclobutylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-2-[5-(5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonylamino)-pyridin-2-yl]-acetamide (15%) as a light brown solid; LRMS for C29H31ClFN7O5S (M+H)+ at m/z=645.

Workup

  1. customAt this time, the N,N,-dimethylformamide was removed in vacuo
  2. customThe residue was triturated with chloroform
  3. custommethanol to remove impurities

Sources & evidence

ORD record
ord-02770daeb0d642c380c763a1f0d776d1
Source dataset
uspto-grants-2006_12
Patent number
US07148229B2

Reaction notes

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