Trifluoroacetic acid → 1-(4-{[6-(3-Aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)ethanone trihydrochloride

HRID 2178848Notes

Reaction equation

HRID 2178848 reaction equation
C(OC(=O)[NH:7][CH: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]([Cl: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:37].[ClH:37].[ClH:37].[NH2:7][CH: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:32]=[C:33]([Cl:39])[C:34]([OH:38])=[C:35]([Cl:37])[CH:36]=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

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136927345Tert-butyl [1-(5-{[3-acetyl-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-4-yl]amino}pyridin-2-yl)piperidin-3-yl]carbamate

Product 1

HCID 1362666401-(4-{[6-(3-Aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)ethanone trihydrochlorideYield 98%

Procedure

Following general procedure IV-2, tert-butyl[1-(5-{[3-acetyl-6-(3,5-dichloro-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 (31 mg, 30% over two steps) as an orange solid: 1H NMR (500 MHz, CD3OD) δ 9.38 (s, 1H), 8.49 (d, J=9.0 Hz, 1H), 8.41 (d, J=9.0 Hz, 1H), 8.25 (d, J=2.6 Hz, 1H), 7.92-7.86 (m, 1H), 7.58 (s, 2H), 7.24 (d, J=9.5 Hz, 1H), 4.41-4.34 (m, 1H), 4.03-3.96 (m, 1H), 3.53-3.32 (m, 4H), 2.84 (s, 3H), 2.24-2.21 (m, 1H), 2.05-1.97 (m, 1H), 1.84-1.76 (m, 2H); ESI MS m/z 523 [M+H]+; HPLC 98.0% (AUC), tR=9.48 min.

Sources & evidence

ORD record
ord-b3d5e9d74f2244649fc0282e482791a8
Source dataset
uspto-grants-2015_06
Patent number
US09067937B2

Reaction notes

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