Trifluoroacetic acid → (S)-1-(4-{[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trihydrochloride

HRID 2178948Notes

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]([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:43])[CH2:41][CH3:42])=[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][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: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:43])[CH2:41][CH3:42])=[CH:18][CH:19]=2)[CH2:9]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 136981881(S)-tert-butyl(1-(5-((6-(3,5-dichloro-4-hydroxyphenyl)-3-propionyl-1,5-naphthyridin-4-yl)amino)pyridin-2-yl)piperidin-3-yl)carbamate

Product 1

HCID 137231122(S)-1-(4-{[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trihydrochlorideYield 247.4%

Procedure

Following general procedure IV-2, (S)-tert-butyl(1-(5-((6-(3,5-dichloro-4-hydroxyphenyl)-3-propionyl-1,5-naphthyridin-4-yl)amino)pyridin-2-yl)piperidin-3-yl)carbamate (0.195 mmol) was reacted with TFA (2 mL) followed by formation of the trihydrochloride salt to afford the desired product (78 mg, 62% over two steps) as an orange-brown solid: 1H NMR (500 MHz, CD3OD) δ 9.32 (s, 1H), 8.47 (d, J=9.0 Hz, 1H), 8.37 (d, J=9.0 Hz, 1H), 8.20 (d, J=2.5 Hz, 1H), 7.76 (dd, J=9.0, 2.5 Hz, 1H), 7.61 (s, 2H), 7.11 (d, J=9.0 Hz, 1H), 4.41-4.38 (m, 1H), 3.97-3.95 (m, 1H), 3.48-3.16 (m, 5H), 2.24-2.15 (m, 1H), 2.03-1.91 (m, 1H), 1.82-1.74 (m, 2H), 1.32-1.19 (m, 3H); ESI MS m/z 537 [M+H]+; HPLC>99% (AUC), tR=9.92 min.

Sources & evidence

ORD record: ord-9590ac3d17f747618a45a5fdb8475208
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067937B2

Reaction notes

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