Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate → Tert-butyl (3-((5-fluoro-2-((3-hydroxy-4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate

HRID 1482682Notes

Reaction equation

HRID 1482682 reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([NH:20][C:21]2[N:26]=[C:25]([NH:27][C:28]3[CH:29]=[C:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH:31]=[CH:32][CH:33]=3)[C:24]([F:42])=[CH:23][N:22]=2)[CH:12]=[CH:13][C:14]=1[O:15][CH2:16][CH2:17][O:18][CH3:19])C1C=CC=CC=1>[Pd].C(O)C>[F:42][C:24]1[C:25]([NH:27][C:28]2[CH:29]=[C:30]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:39])([CH3:38])[CH3:40])[CH:31]=[CH:32][CH:33]=2)=[N:26][C:21]([NH:20][C:11]2[CH:12]=[CH:13][C:14]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[C:9]([OH:8])[CH:10]=2)=[N:22][CH:23]=1

Participants

4

Reactant 1

HCID 86724337Tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate

Product 1

HCID 86724338Tert-butyl (3-((5-fluoro-2-((3-hydroxy-4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamateYield 81.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

In a 100 mL Autoclave, Pd—C (0.035 g) and ethanol were charged. tert-butyl (3-((2-((3-(benzyloxy)-4-(2-methoxyethoxy)phenyl)amino)-5-fluoropyrimidin-4-yl)amino)phenyl)carbamate (0.35 g) was added to the above reaction mixture, and the autoclave was flushed with nitrogen. Hydrogen pressure (140 psi) was applied and reaction mixture was stirred at room temperature for 50 hr. After completion, the reaction mixture was filtered using Celite and the filter cake was washed with ethanol. The filtrate was concentrated under reduced pressure at 40° C. to give 0.240 g of tert-butyl (3-((5-fluoro-2-((3-hydroxy-4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)carbamate. 1H NMR: DMSO-d6 (400 MHz): 1.475 (s, 9H), 3.316 (s, 3H), 3.618-3.641 (t, 2H, J=4.4), 4.028-4.050 (t, 2H, J=4.4), 6.732-6.753 (d, 1H, J=8.4), 7.075-7.097 (m, 2H), 7.141-7.208 (m, 2H), 7.476-7.495 (d, 1H, J=7.6), 7.851 (s, 1H), 8.036-8.045 (d, 1H, J=3.6), 8.784-8.796 (d, 2H, J=4.8), 9.260-9.301 (d, 2H, J=16.4).

Workup

  1. customthe autoclave was flushed with nitrogen
  2. customreaction mixture
  3. filtrationAfter completion, the reaction mixture was filtered
  4. washthe filter cake was washed with ethanol
  5. concentrationThe filtrate was concentrated under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-a33fe26b7d154365b80713313f728941
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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