Sodium ethoxide → HCID 58765485, compound

HRID 861146Notes

Reaction equation

HRID 861146 reaction equation
Cl.[CH:2]1([NH:7][C:8]([NH2:10])=[NH:9])[CH2:6][CH2:5][CH2:4][CH2:3]1.[O-]CC.[Na+].[Cl:15][C:16]1[N:21]2[N:22]=[C:23]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=3)[C:24]([C:25](=O)/[C:26](/[CH3:29])=[CH:27]/[CH3:28])=[C:20]2[CH:19]=[CH:18][CH:17]=1.ClC1N2N=C(C3C=CC=C(C)C=3)C(C(=O)/C(/C)=C\C)=C2C=CC=1>C(O)C.[Pd]>[Cl:15][C:16]1[N:21]2[N:22]=[C:23]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=3)[C:24]([C:25]3[C:26]([CH3:29])=[C:27]([CH3:28])[N:10]=[C:8]([NH:7][CH:2]4[CH2:6][CH2:5][CH2:4][CH2:3]4)[N:9]=3)=[C:20]2[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 2723922Sodium ethoxideHCID 57444740HCID 57444740, compoundHCID 57444741HCID 57444741, compoundHCID 178479367HCID 178479367, compound

Product 1

HCID 58765485HCID 58765485, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

To a suspension of N-cyclopentylguanidine hydrochloride (261 mg, 1.60 mmol) in ethanol (2 mL) was added sodium ethoxide (530 μL, 3 M in ethanol, 1.6 mmol). The mixture was stirred at room temperature for 10 minutes. To this suspension was added a mixture of (2E)-1-[7-chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-methyl-2-buten-1-one and (2Z)-1-[7-chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-methyl-2-buten-1-one (200 mg, 0.616 mmol) portionwise. The reaction mixture was stirred at 70° C. for 16 hours then cooled to room temperature. Palladium on carbon (10%, 230 mg) was added and the reaction mixture was stirred at 60° C. for 24 hours. The reaction mixture was diluted with ethanol (15 mL) and filtered through Celite. The filtrate was concentrated in vacuo and chromatographed (39:1 dichloromethane:methanol) to provide 4-[7-chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-N-cyclopentyl-5,6-dimethyl-2-pyrimidinamine (80 mg, 30%) as a light brown solid. Rf 0.47 (29:1 dichloromethane:methanol); 1H NMR (CDCl3) δ 7.60 (s, 1H), 7.55 (d, 1H), 7.32 (d, 1H), 7.21–7.11 (m, 3H), 6.96 (d, 1H), 4.99 (broad, 1H), 4.28 (m, 1H); 2.35 (s, 3H), 2.30 (s, 3H), 2.01 (m, 2H), 1.74–1.42 (9 H); MS m/z 432 (M+1).

Workup

  1. additionTo this suspension was added
  2. stirringThe reaction mixture was stirred at 70° C. for 16 hours
  3. temperaturethen cooled to room temperature
  4. stirringthe reaction mixture was stirred at 60° C. for 24 hours
  5. filtrationfiltered through Celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. customchromatographed (39:1 dichloromethane:methanol)

Sources & evidence

ORD record
ord-b100a5abe6ef4525bcf413d115dfd275
Source dataset
uspto-grants-2006_12
Patent number
US07153855B2

Reaction notes

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