Trifluoroacetic acid → (R)-1-(4-((6-(3-aminopiperidin-1-yl)pyridin-3-yl)amino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trichloride

HRID 2178953Notes

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:43])[CH2:41][CH3:42])=[CH:16][N:15]=2)[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>>[Cl-:39].[Cl-:39].[Cl-: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:43])[CH2:41][CH3:42])=[CH:18][CH:19]=2)[CH2:9]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 136981877(R)-tert-butyl (1-(5-((6-(3-chloro-5-fluoro-4-hydroxyphenyl)-3-propionyl-1,5-naphthyridin-4-yl)amino)pyridin-2-yl)piperidin-3-yl)carbamate

Product 1

HCID 137231125(R)-1-(4-((6-(3-aminopiperidin-1-yl)pyridin-3-yl)amino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trichlorideYield 261.8%

Procedure

Following general procedure IV-2, (R)-tert-butyl(1-(5-((6-(3-chloro-5-fluoro-4-hydroxyphenyl)-3-propionyl-1,5-naphthyridin-4-yl)amino)pyridin-2-yl)piperidin-3-yl)carbamate (120 mg, 0.19 mmol) was reacted with TFA (2 mL) followed by formation of the trihydrochloride salt to afford the desired product (78 mg, 65%) as a orange-brown solid: 1H NMR (500 MHz, CD3OD) δ 9.38 (s, 1H), 8.48 (d, J=9.0 Hz, 1H), 8.41 (d, J=9.0 Hz, 1H), 8.25 (d, J=2.5 Hz, 1H), 7.90 (dd, J=9.5, 2.5 Hz, 1H), 7.56-7.30 (m, 2H), 7.27 (d, J=9.5 Hz, 1H), 4.43-4.32 (m, 1H), 4.08-3.96 (m, 1H), 3.53-3.38 (m, 3H), 3.29-3.20 (m, 2H), 2.29-2.20 (m, 1H), 2.09-1.98 (m, 1H), 1.88-1.74 (m, 2H), 1.38-1.21 (m, 3H); ESI MS m/z 521 [M+H]+; HPLC 97.6% (AUC), tR=9.86 min.

Sources & evidence

ORD record: ord-4b43dac3732741b2a7515e1d8407512e
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067937B2

Reaction notes

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