Cesium carbonate → tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

HRID 1779089Notes

Reaction equation

HRID 1779089 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[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[N:24][N:25]([CH:27]2[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]2)[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:19][C:17](=[O:18])[CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][CH2:8][C:6]1[C:5]([CH3:20])=[CH:4][N:3]=[C:2]([NH:21][C:22]2[CH:23]=[N:24][N:25]([CH:27]3[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]3)[CH:26]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 272815264-Amino-1-(1-Boc-azetidin-3-yl)-1H-pyrazole2×HCID 867126242-(2-(2-Chloro-5-methylpyrimidin-4-ylethyl)phenyl)acetamide

Product 1

HCID 86712726tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A suspension of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide (K6) (0.150 g, 0.518 mmol), 4-amino-1-(1-Boc-azetidin-3-yl)-1H-pyrazole (0.195 g, 0.777 mmol), Pd(OAc)2 (2.3 mg, 0.010 mmol), Cs2CO3 (0.506 g, 1.55 mmol) and Xantphos (11.9 mg, 0.021 mmol) in 1,4-dioxane (2 mL) was heated under microwave irradiation at 100° C. for 1.5 hours. 4-Amino-1-(1-Boc-azetidin-3-yl)-1H-pyrazole (65.0 mg, 0.259 mmol) was added and the mixture was heated for a further 1 hour at 100° C. The resulting mixture was adsorbed onto silica gel and purified using column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-5% MeOH in DCM) to give the title compound A120 as a light pink colored foam (0.050 g, 19%); 1H NMR (300 MHz, d4-MeOH) δ 8.06 (d, J=8.8 Hz, 2H), 7.66 (s, 1H), 7.16-7.27 (m, 4H), 5.12-5.21 (m, 1H), 4.39 (t, J=8.7 Hz, 2H), 4.25-4.30 (m, 2H), 3.65 (s, 2H), 3.32 (s, 1H), 3.10-3.16 (m, 2H), 2.95-3.00 (m, 2H), 2.10 (s, 3H), 1.48 (s, 9H). LCMS-B: rt 6.184 min; m/z 492 [M+H]+.

Workup

  1. temperaturethe mixture was heated for a further 1 hour at 100° C
  2. custompurified

Sources & evidence

ORD record
ord-23396d436578482087f13caf21bd120c
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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