Acetic Acid → HCID 178474561, compound

HRID 2189834Notes

Reaction equation

[NH2:1][CH2:2][C:3]1[C:4]([NH:20][C@H:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:22][OH:23])=[N:5][C:6]([NH:10][C:11]2[CH:15]=[C:14]([O:16][CH:17]([CH3:19])[CH3:18])[NH:13][N:12]=2)=[C:7]([F:9])[CH:8]=1.[C:31](O)(=[O:33])[CH3:32]>C1COCC1.C(Cl)Cl>[F:9][C:7]1[CH:8]=[C:3]([CH2:2][NH:1][C:31](=[O:33])[CH3:32])[C:4]([NH:20][C@H:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[CH2:22][OH:23])=[N:5][C:6]=1[NH:10][C:11]1[CH:15]=[C:14]([O:16][CH:17]([CH3:19])[CH3:18])[NH:13][N:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

(R)-2-(3-(Aminomethyl)-5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)pyridin-2-ylamino)-2-(4-fluorophenyl)ethanol (Example 13; 0.175 g, 0.42 mmol) and acetic acid loaded TFP resin (1.4 mmol/g loading, 0.42 mmol) were placed in a THF-DCM solution (1:1, 5 ml) at 0° C. The resulting solution was shaken vigorously at 0° C. for 45 min and filtered. The resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each). The resulting organic layers were combined and concentrated. The resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml) to give the title compound (0.075 g, 39%). 1H NMR (400 MHz, CD3OD) δ 7.42-7.39 (m, 2H), 7.17 (d, J=10.7 Hz, 1H), 7.05-7.01 (m, 2H), 5.26 (s, 1H), 5.02-4.95 (m, 1H), 4.55-4.53 (m, 1H), 4.36 (d, J=15.0 Hz, 1H), 4.22 (d, J=15.0 Hz, 1H), 3.84-3.72 (m, 2H), 2.01 (s, 3H), 1.31 (d, J=6.0 Hz, 6H). MS: Calcd.: 460. Found: [M+H]+ 461.

Workup

filtrationfiltered
washThe resulting resin was washed with a THF-DCM solution (1:1, 3×5 ml for 30 min. each)
concentrationconcentrated
customThe resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml)

Sources & evidence

ORD record: ord-94dd364d891448989b2d26f896e443ae
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08324252B2

Reaction notes

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