Cesium carbonate → tert-Butyl 4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)benzylcarbamate

HRID 1779080Notes

Reaction equation

HRID 1779080 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.[C:21]([NH:28][CH2:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].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:34][C:33]2[CH:35]=[CH:36][C:30]([CH2:29][NH:28][C:21](=[O:22])[O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[CH:31][CH:32]=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 2756041tert-butyl N-[(4-aminophenyl)methyl]carbamateHCID 86712624HCID 86712624, compound

Product 1

HCID 86712717tert-Butyl 4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-methylpyrimidin-2-yl)amino)benzylcarbamate

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-(N-Boc-aminomethyl)aniline (0.145 g, 0.621 mmol), Pd(OAc)2 (2.3 mg, 0.010 mmol), Cs2CO3 (0.506 g, 1.55 mmol) and Xantphos (12 mg, 0.021 mmol) in 1,4-dioxane (2 mL) was heated under microwave irradiation at 100° C. for 1.5 hours. The resulting mixture was filtered through a plug of silica gel, washing with 10% MeOH in DCM. The volatiles were removed in vacuo and the residue was adsorbed onto silica gel and the product purified using silica gel column chromatography (CombiFlash Rf, 12 g SiO2 cartridge, 0-5% MeOH in DCM) to give the title compound A114 as a white solid (0.043 g, 17%); 1H NMR (300 MHz, d4-MeOH) δ 8.07 (brs, 1H), 7.59 (brs, 2H), 7.19 (m, 6H), 4.19 (brs, 2H), 3.64 (brs, 2H), 3.11 (brs, 2H), 2.95-2.98 (m, 2H), 2.08 (brs, 3H), 1.46 (brs, 9H). LCMS-B: rt 6.636 min; m/z 476 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through a plug of silica gel
  2. washwashing with 10% MeOH in DCM
  3. customThe volatiles were removed in vacuo
  4. customthe product purified

Sources & evidence

ORD record
ord-7c106388c7e84bd58f0797ef7ae69897
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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