Cesium carbonate → Methyl 1-(4-(4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-ylamino)phenyl)cyclobutylcarbamate

HRID 1779088Notes

Reaction equation

HRID 1779088 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.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+].[NH2:69][C:70]1[CH:75]=[CH:74][C:73]([C:76]2([NH:80][C:81](=[O:84])[O:82][CH3:83])[CH2:79][CH2:78][CH2:77]2)=[CH:72][CH:71]=1>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:69][C:70]2[CH:71]=[CH:72][C:73]([C:76]3([NH:80][C:81](=[O:84])[O:82][CH3:83])[CH2:77][CH2:78][CH2:79]3)=[CH:74][CH:75]=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 867126242-(2-(2-Chloro-5-methylpyrimidin-4-ylethyl)phenyl)acetamideHCID 86712724Methyl 1-(4-aminophenyl)cyclobutylcarbamate

Product 1

HCID 86712725Methyl 1-(4-(4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-ylamino)phenyl)cyclobutylcarbamateYield 35.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A suspension of 2-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)acetamide (K6) (150 mg, 0.518 mmol), Pd(OAc)2 (11.6 mg, 0.052 mmol), Xantphos (45.0 mg, 0.078 mmol), Cs2CO3 (486 mg, 1.49 mmol) and methyl 1-(4-aminophenyl)cyclobutylcarbamate (A119) (125 mg, 0.569 mmol) in 1,4-dioxane (4.0 mL) was heated under microwave irradiation for 10 minutes at 150° C. The resulting mixture was filtered through Celite, and washed with EtOAc. The filtrate was concentrated under reduced pressure and the residue was purified by semi preparative HPLC to give the title compound 29 (86 mg, 35%); 1H NMR (300 MHz, CDCl3): δ 8.17 (br s, 1H), 7.56 (m, 2H), 7.42 (m, 2H), 7.28 (4H, obscured by solvent peak), 5.65 (br s, 1H), 5.42 (br s, 1H), 5.30 (br s, 1H), 3.70 (s, 2H), 3.61 (s, 3H), 3.13 (m, 2H), 2.99 (m, 2H), 2.57 (s, 3H), 2.12-1.62 (m, 6H). LCMS-B: rt 6.28 min; m/z 474.2 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashed with EtOAc
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe residue was purified by semi preparative HPLC

Sources & evidence

ORD record
ord-21ad8007265a4ce48aa86acbe51330fa
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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