Trifluoroacetic acid → (S)-1-(4-{[6-(3-Aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3-chloro-5-fluoro-4-hydroxy-phenyl)-1,5-naphthyridin-3-yl)ethanone trihydrochloride

HRID 2178855Notes

Reaction equation

C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[CH:36]=[C:35]([F:37])[C:34]([OH:38])=[C:33]([Cl:39])[CH:32]=5)[N:29]=4)[N:24]=[CH:23][C:22]=3[C:40](=[O:42])[CH3:41])=[CH:16][N:15]=2)[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>>[ClH:39].[ClH:39].[ClH:39].[NH2:7][C@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[N:15]=[CH:16][C:17]([NH:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[CH:36]=[C:35]([F:37])[C:34]([OH:38])=[C:33]([Cl:39])[CH:32]=5)[N:29]=4)[N:24]=[CH:23][C:22]=3[C:40](=[O:42])[CH3:41])=[CH:18][CH:19]=2)[CH2:9]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 136981872(S)-tert-butyl [1-(5-{[3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-4-yl]amino}pyridin-2-yl)piperidin-3-yl]carbamate

Product 1

HCID 136266666(S)-1-(4-{[6-(3-Aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3-chloro-5-fluoro-4-hydroxy-phenyl)-1,5-naphthyridin-3-yl)ethanone trihydrochlorideYield 136.3%

Procedure

Following general procedure IV-2, (S)-tert-butyl[1-(5-{[3-acetyl-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-4-yl]amino}pyridin-2-yl)piperidin-3-yl]carbamate (0.20 mmol) was reacted with TFA (2 mL) followed by formation of the trihydrochloride salt to afford the desired product (42 mg, 34% over two steps) as an orange-yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.30 (s, 1H), 8.45 (d, J=9.0 Hz, 1H), 8.35 (d, J=9.0 Hz, 1H), 8.19 (d, J=2.6 Hz, 1H), 7.68 (dd, J=9.2, 2.6 Hz, 1H), 7.45 (br s, 1H), 7.27 (br s, 1H), 7.05 (d, J=9.2 Hz, 1H), 4.43-4.36 (m, 1H), 3.94-3.92 (m, 1H), 3.44-3.32 (m, 3H), 2.81 (s, 3H), 2.23-2.15 (m, 1H), 2.05-1.91 (m, 1H), 1.77-1.73 (m, 2H); ESI MS m/z 507 [M+H]+; HPLC>99% (AUC), tR=9.57 min.

Sources & evidence

ORD record: ord-59533ee57cf94cb6a315c519844454ae
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067937B2

Reaction notes

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