Cesium carbonate → (2-Chloro-pyridin-4-yl)-(5-cyclopropyl-1H-pyrazole-3-yl)-amine

HRID 2189881Notes

Reaction equation

I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.C(OC([N:16]1[C:20]([CH:21]2[CH2:23][CH2:22]2)=[CH:19][C:18]([NH2:24])=[N:17]1)=O)(C)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:4]1[CH:3]=[C:2]([NH:24][C:18]2[CH:19]=[C:20]([CH:21]3[CH2:23][CH2:22]3)[NH:16][N:17]=2)[CH:7]=[CH:6][N:5]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-iodo-2-chloropyridine (0.26 g, 1.1 mmol), 3-amino-5-cyclopropyl-pyrazole -1-carboxylic acid tert-butyl ester (0.20 g, 0.89 mmol), Pd2dba3 (0.016 g, 2 mol %), Xantphos (0.031 g, 6 mol %), and Cs2CO3 (0.41 g, 1.3 mmol) in degassed toluene (4 ml) was purged with N2 and heated to 100° C. in a sealed tube for 2 days. The mixture was diluted with THF and filtered to remove Cs2CO3. The filtrate was concentrated under reduced pressure and purified by column chromatography (hexane-EtOAc=3:1) to give the title compound (0.10 g, 48%). MS: Calcd.: 234. Found: [M+H]+ 235.

Workup

customwas purged with N2
additionThe mixture was diluted with THF
filtrationfiltered
customto remove Cs2CO3
concentrationThe filtrate was concentrated under reduced pressure
custompurified by column chromatography (hexane-EtOAc=3:1)

Sources & evidence

ORD record: ord-ebae0cafc95940d2941f2a2f428e7334
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324252B2

Reaction notes

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