HCID 86712706, compound → HCID 86712707, compound

HRID 1779064Notes

Reaction equation

HRID 1779064 reaction equation
[CH3:1][O:2][C:3]1[C:4]([C:29]#[C:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[CH2:37][C:38]([O:40][CH3:41])=[O:39])=[N:5][C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:12][CH:11]=2)=[N:7][CH:8]=1>CN(C=O)C.[Pd]>[CH3:1][O:2][C:3]1[C:4]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[CH2:37][C:38]([O:40][CH3:41])=[O:39])=[N:5][C:6]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:14][CH:15]=2)=[N:7][CH:8]=1

Participants

4

Reactant 1

HCID 86712706HCID 86712706, compound

Product 1

HCID 86712707HCID 86712707, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A slurry of 10% Pd/C (53% water; 0.100 g) in DMF (2 mL) was added to a solution of tert-butyl 4-(4-((5-methoxy-4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A99) (0.112 g, 0.201 mmol) in DMF (8 mL) and TEA (1 mL), and the resulting mixture stirred under an atmosphere of hydrogen at room temperature for 16 hours. The resulting mixture was filtered through a pad of Celite, washing with EtOAc (50 mL). The solvent was removed in vacuo and the resultant residue purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-65% EtOAc in petroleum benzine 40-60° C.) to yield the title compound A100 as a pale yellow oil (0.110 g, 98%); 1H NMR (400 MHz, CDCl3) δ 7.95 (s, 1H), 7.50 (d, J=8.6 Hz, 2H), 7.24-7.14 (m, 4H), 7.11 (d, J=8.5 Hz, 2H), 7.02 (s, 1H), 4.34-4.13 (m, 2H), 3.76 (s, 3H), 3.73 (s, 2H), 3.65 (s, 3H), 3.06-2.98 (m, 2H), 2.98-2.90 (m, 2H), 2.77 (t, J=12.1 Hz, 2H), 2.58 (tt, J=11.9, 3.3 Hz, 1H), 1.78 (d, J=13.0 Hz, 2H), 1.57 (qd, J=12.9, 4.5 Hz, 2H), 1.46 (s, 9H). LCMS-A: rt 6.77 min; m/z 561.4 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through a pad of Celite
  2. washwashing with EtOAc (50 mL)
  3. customThe solvent was removed in vacuo
  4. customthe resultant residue purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-65% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-fa887a5794d34492b24925ead6dc837e
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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