Benzyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)benzoate → 4-[(3-{8-[(3,4-Dimethoxyphenyl)amino]imidazo[1,2-A]pyrazin-6-Yl}benzoyl)amino]benzoic Acid

HRID 2365468Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:14]([CH:43]=[CH:44][N:45]=3)[CH:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:40]=[CH:41][CH:42]=3)[C:21]([NH:23][C:24]3[CH:39]=[CH:38][C:27]([C:28]([O:30]CC4C=CC=CC=4)=[O:29])=[CH:26][CH:25]=3)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]>C(OCC)(=O)C.C(O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:14]([CH:43]=[CH:44][N:45]=3)[CH:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:40]=[CH:41][CH:42]=3)[C:21]([NH:23][C:24]3[CH:39]=[CH:38][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=3)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of benzyl 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)benzoate (1.75 g, 2.92 mmol) in ethyl acetate (500 mL) and ethanol (500 mL) at 60° C. was treated with 10% palladium on carbon (5.11 g, 50% water by weight) and sparged with hydrogen for 30 min at 60° C. then stirred under balloon pressure hydrogen at 60° C. for 30 min. After this time, the reaction was sparged with nitrogen for 10 min and filtered hot through diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue obtained was exhaustively triturated: boiling acetonitrile (50 mL×2); then boiling methanol (50 mL); then boiling 1:1 methanol/acetonitrile (50 mL); then boiling acetonitrile (50 mL); then boiling 1:1 methanol/acetonitrile (50 mL) to afford 4-(3-(8-(3,4-dimethoxyphenylamino)imidazo[1,2-a]pyrazin-6-yl)benzamido)benzoic acid (458 mg, 31%) as an off-white solid: mp>250° C.; 1H NMR (300 MHz, DMSO-d6) δ 12.74 (br s, 1H), 10.67 (s, 1H), 9.57 (s, 1H), 8.74 (s, 1H), 8.56 (s, 1H), 8.25 (d, J=7.8 Hz, 1H), 8.80-7.89 (m, 7H), 7.69-7.53 (m, 3H), 6.93 (d, J=8.7 Hz, 1H), 3.78 (s, 3H), 3.71 (s, 3H); ESI MS m/z 510 [M+H]+; HPLC, 6.50 min, 95.6% (AUC).

Workup

customsparged with hydrogen for 30 min at 60° C.
customAfter this time, the reaction was sparged with nitrogen for 10 min
filtrationfiltered hot through diatomaceous earth
concentrationThe filtrate was concentrated under reduced pressure
customthe residue obtained
customwas exhaustively triturated

Sources & evidence

ORD record: ord-f1674676f6824979a6cdf9adfd51aa1a
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697699B2

Reaction notes

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