Cesium carbonate → tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 592437Notes

Reaction equation

HRID 592437 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][N:27]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)[CH:28]=1.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+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([CH3:22])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:25]=[N:26][N:27]([CH:29]4[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]4)[CH:28]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27281520tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylateHCID 867123151-(2-(2-(2-Chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 86712317tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A40 (0.250 g, 0.792 mmol), tert-butyl 4-(4-amino-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.422 g, 1.58 mmol), Pd(OAc)2 (0.004 g, 0.016 mmol), Xantphos (0.018 g, 0.032 mmol) and Cs2CO3 (0.774 g, 2.38 mmol) in dioxane (15 mL) was bubbled with N2 for 10 minutes and then stirred in the microwave at 120° C. for 20 minutes. The volatiles were removed in vacuo and the residue was adsorbed onto SiO2 and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A43 as a brown solid (0.118 g, 27%). LCMS-D: rt 3.40 min; m/z 546 [M+H]+.

Workup

  1. customwas bubbled with N2 for 10 minutes
  2. customThe volatiles were removed in vacuo
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-a86fa809e2df420ea7c00b64eb0189a0
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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