D-Psicose → HCID 86712713, compound

HRID 1779071Notes

Reaction equation

HRID 1779071 reaction equation
[CH3:1][O:2][C:3](=[O:47])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[C:15]#[C:16][C:17]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[N:18]=1.OCC1(OC[C@@H](O)[C@@H](O)[C@H]1O)O>CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:47])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:8]=[CH:7][C:6]=1[CH2:15][CH2:16][C:17]1[C:22]([C:23]([F:25])([F:26])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[N:18]=1

Participants

5

Reactant 2

HCID 441036D-PsicoseHCID 86712712HCID 86712712, compound

Product 1

HCID 86712713HCID 86712713, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A suspension of 10% Pd/C (0.050 g) and tert-butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)-4-(trifluoromethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A106) (0.196 g, 0.295 mmol) in DMF (20 mL) was stirred under a hydrogen atmosphere at 50 Psi pressure for 24 hours. The resulting mixture was filtered through Celite, washing with MeOH (2×50 mL). The filtrate was adsorbed onto silica gel then purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound A107 as a light yellow liquid (0.157 g, 80%); 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.52-7.43 (m, 3H), 7.35 (d, J=7.8 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 4.25 (brs, 2H), 3.79 (s, 2H), 3.70 (s, 3H), 3.17 (m, 2H), 3.09 (m, 2H), 2.81 (t, J=11.4 Hz, 2H), 2.70-2.56 (m, 1H), 1.83 (d, J=12.7 Hz, 2H), 1.72-1.55 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 7.199 min; m/z 667.3 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashing with MeOH (2×50 mL)
  3. customthen purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-b721a227fbe643379280b77193efb370
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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