Cesium carbonate → HCID 86712727, compound

HRID 1779091Notes

Reaction equation

HRID 1779091 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][S:81]([C:83]([CH3:86])([CH3:85])[CH3:84])=[O:82])[CH2:79][O:78][CH2:77]2)=[CH:72][CH:71]=1>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:85][C:83]([CH3:86])([S:81]([NH:80][C:76]1([C:73]2[CH:74]=[CH:75][C:70]([NH:69][C:2]3[N:7]=[C:6]([CH2:8][CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[CH2:16][C:17]([NH2:19])=[O:18])[C:5]([CH3:20])=[CH:4][N:3]=3)=[CH:71][CH:72]=2)[CH2:79][O:78][CH2:77]1)=[O:82])[CH3:84]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58345210HCID 58345210, compoundHCID 867126242-(2-(2-Chloro-5-methylpyrimidin-4-ylethyl)phenyl)acetamide

Product 1

HCID 86712727HCID 86712727, compound

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) (200 mg, 0.690 mmol), Pd(OAc)2(16 mg, 0.069 mmol), Xantphos (59.9 mg, 0.104 mmol), Cs2CO3 (648 mg, 1.99 mmol) and N-(3-(4-aminophenyl)oxetan-3-yl)-2-methylpropane-2-sulfinamide (A121) (204 mg, 0.759 mmol) in 1,4-dioxane (1.73 mL) was heated under microwave irradiation for 10 minutes at 150° C. under nitrogen. The resulting mixture was filtered through Celite, washing with EtOAc. The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-30% MeOH in DCM) to give the title compound A122 (102 mg, 28%); 1H NMR (300 MHz, d4-MeOH) δ 8.07 (s, 1H), 7.74 (d, J=8.6 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.19 (m, 4H), 5.17 (d, J=6.6 Hz, 1H), 5.07 (d, J=6.5 Hz, 1H), 5.03 (d, J=6.7 Hz, 1H), 4.93 (d, J=6.4 Hz, 1H), 3.64 (s, 2H), 3.12 (m, 2H), 2.95 (m, 2H), 2.07 (s, 3H), 1.27 (s, 9H). LCMS-B: rt 5.80 min; 522.2 m/z [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashing with EtOAc
  3. customThe volatiles were removed in vacuo
  4. customthe residue was purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-30% MeOH in DCM)

Sources & evidence

ORD record
ord-aa06896e2e034fe8bc9d36766b92a628
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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