Benzyl 2-(4-(4-(5-((5-(tert-butyl)oxazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate → 2-(4-(4-(5-((5-(Tert-butyl)oxazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetic acid

HRID 881741Notes

Reaction equation

HRID 881741 reaction equation
[C:1]([C:5]1[O:9][C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]45[CH2:30][CH2:29][C:26]([CH2:31][C:32]([O:34]CC6C=CC=CC=6)=[O:33])([CH2:27][CH2:28]4)[O:25][CH2:24]5)=[CH:19][CH:18]=3)=[N:15][CH:16]=2)=[N:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>CCOC(C)=O.C1COCC1.[OH-].[OH-].[Pd+2]>[C:1]([C:5]1[O:9][C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]45[CH2:28][CH2:27][C:26]([CH2:31][C:32]([OH:34])=[O:33])([CH2:29][CH2:30]4)[O:25][CH2:24]5)=[CH:19][CH:18]=3)=[N:15][CH:16]=2)=[N:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 86700843Benzyl 2-(4-(4-(5-((5-(tert-butyl)oxazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

Product 1

HCID 721884312-(4-(4-(5-((5-(Tert-butyl)oxazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetic acidYield 33.5%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

Benzyl 2-(4-(4-(5-((5-(tert-butyl)oxazol-2-yl)amino)pyridin-2-yl)phenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (100 mg, 0.181 mmol) was dissolved in EtOAc/THF and hydrogenated with 10% Pd(OH)2/C under H2 balloon for 3 hr. The reaction mixture was filtered and the filtrate was concentrated. The residue was purified by prep-HPLC to give the title compound (28 mg, 31.5% yield). HR/MS [M+H]+: found 462.2390. calc. 462.2393. RT: 2.83 (Condition L). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.26 (s, 9H), 1.86-2.03 (m, 8H), 2.32 (s, 2H), 3.90 (s, 2H), 6.60 (s, 1H), 7.39 (d, J=8.59 Hz, 2H), 7.87 (d, J=8.59 Hz, 1H), 7.95 (d, J=8.59 Hz, 2H), 8.15 (dd, J=8.84, 2.78 Hz, 1H), 8.77 (d, J=2.78 Hz, 1H), 10.36 (br. s., 1H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-dd82dc2045a74caa8d383768985f6170
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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