1,1'-Carbonyldiimidazole → N'-({2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}oxy)pyrimidine-2-carboximidamide

HRID 2074102Notes

Reaction equation

HRID 2074102 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([OH:15])=[O:14])[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.O[N:37]=[C:38]([C:40]1[N:45]=[CH:44][CH:43]=[CH:42][N:41]=1)[NH2:39]>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[N:11]([CH2:12][C:13]([O:15][N:37]=[C:38]([C:40]3[N:45]=[CH:44][CH:43]=[CH:42][N:41]=3)[NH2:39])=[O:14])[N:10]=[C:9]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[CH:8]=2)=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 670925255-[(4-fluorophenyl)methyl]-3-(4-pyridinyl)-1H-Pyrazole-1-acetic acidHCID 136195713N'-hydroxypyrimidine-2-carboximidamide

Product 1

HCID 86617958N'-({2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}oxy)pyrimidine-2-carboximidamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of [5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetic acid (200 mg, 0.64 mmol) in THF (2 mL) and DMF (2 mL) was added CDI (240 mg, 1.41 mmol) and stirred for 2 hours forming a clear solution. To this was added N′-hydroxypyrimidine-2-carboximidamide (115 mg, 0.84 mmol) and the resulting suspension stirred for 18 hours at room temperature. The solid was filtered off to yield crude N′-({2-[5-(4-fluorobenzyl)-3-pyridin-4-yl-1H-pyrazol-1-yl]acetyl}oxy)pyrimidine-2-carboximidamide, and suspended in THF (2 mL) and a solution of TBAF (1 M in THF, 0.64 mL, 0.64 mmol) was added and the mixture stirred for 15 minutes at room temperature. The volatiles were then removed in vacuo and the residue purified by Biotage flash chromatography, eluting with 2-6% MeOH/DCM to afford the title compound as a waxy white solid, 100 mg, 37%. 1H NMR (400 MHz, DMSO-D6) δ ppm 9.00 (d, 2 H), 8.56 (d, 2 H), 7.68-7.73 (m, 3 H), 7.27-7.33 (m, 2 H), 7.05 (t, 2 H), 6.77 (s, 1 H), 6.00 (s, 2 H), 4.18 (s, 2 H); m/z (APCI+) for C22H16N7FO 414.1 (M+H)+.

Workup

  1. customforming a clear solution
  2. stirringthe resulting suspension stirred for 18 hours at room temperature
  3. filtrationThe solid was filtered off

Sources & evidence

ORD record
ord-8117a19197114ae1a7c01a344a61e906
Source dataset
uspto-grants-2011_04
Patent number
US07919488B2

Reaction notes

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