Triethylamine → HCID 86712638, compound

HRID 1778968Notes

Reaction equation

HRID 1778968 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][CH:14]=2)[N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.[C:54]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[CH2:62][C:63]([O:65][CH3:66])=[O:64])#[CH:55]>CN(C=O)C.C1(C)C=CC=CC=1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:21]([O:20][C:19]([NH:18][CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([C:55]#[C:54][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[CH2:62][C:63]([O:65][CH3:66])=[O:64])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[CH:14][CH:15]=1)=[O:25])([CH3:24])([CH3:23])[CH3:22]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 575846421,1-Dimethylethyl N-[[4-[[4-chloro-5-(trifluoromethyl)-2-pyrimidinyl]amino]phenyl]methyl]carbamate

Product 1

HCID 86712638HCID 86712638, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of tert-butyl 4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzylcarbamate (A12) (500 mg, 1.24 mmol), CuI (12 mg, 0.06 mmol), PPh3 (16 mg, 0.06 mmol), and Et3N (346 μL, 2.28 mmol) in DMF (3 mL) was sonicated for 5 minutes before the addition of PdCl2(PPh3)2 (44 mg, 0.06 mmol) and methyl 2-(2-ethynylphenyl)acetate (K1) (324 mg, 1.86 mmol). The resulting mixture was heated under microwave irradiation at 120° C. for 20 minutes then adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to yield a yellow solid. The solid was suspended in toluene and the resulting suspension sonicated for 10 minutes. The resulting suspension was filtered and the filter cake dried to give the title compound A13 as a yellow solid (412 mg, 61%); 1H NMR (400 MHz, d6-DMSO) δ 10.44 (s, 1H), 8.82 (s, 1H), 7.68 (d, J=8.4 Hz, 2H), 7.63 (d, J=7.6 Hz, 1H), 7.58-7.52 (m, 1H), 7.50-7.40 (m, 2H), 7.36 (t, J=6.0 Hz, 1H), 7.22 (d, J=8.5 Hz, 2H), 4.10 (d, J=6.0 Hz, 2H), 3.96 (s, 2H), 3.62 (s, 3H), 1.40 (s, 9H). LCMS-A: rt 6.497 min; m/z 539 [M−1]−.

Workup

  1. custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
  2. customto yield a yellow solid
  3. customthe resulting suspension sonicated for 10 minutes
  4. filtrationThe resulting suspension was filtered
  5. customthe filter cake dried

Sources & evidence

ORD record
ord-c421847a993a43f68c8977bcbe7b3d54
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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