Trifluoroacetic acid → (S)-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 trihydrochloride

HRID 526229Notes

Reaction equation

HRID 526229 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[N:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][C:14]([C:20](=[O:23])[CH2:21][CH3:22])=[C:13]3[NH:24][C:25]2[CH:26]=[CH:27][C:28]([N:31]3[CH2:36][CH2:35][CH2:34][C@H:33]([NH:37]C(=O)OC(C)(C)C)[CH2:32]3)=[N:29][CH:30]=2)[CH:5]=[C:6]([F:9])[C:7]=1[OH:8].C(O)(C(F)(F)F)=O>>[ClH:1].[ClH:1].[ClH:1].[NH2:37][C@H:33]1[CH2:34][CH2:35][CH2:36][N:31]([C:28]2[N:29]=[CH:30][C:25]([NH:24][C:13]3[C:12]4[C:17](=[CH:18][CH:19]=[C:10]([C:4]5[CH:5]=[C:6]([F:9])[C:7]([OH:8])=[C:2]([Cl:1])[CH:3]=5)[N:11]=4)[N:16]=[CH:15][C:14]=3[C:20](=[O:23])[CH2:21][CH3:22])=[CH:26][CH:27]=2)[CH2:32]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136981882(S)-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 137231123(S)-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 trihydrochlorideYield 202.5%

Procedure

Following general procedure IV-2, (S)-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 (0.21 mmol) was reacted with TFA (2 mL) followed by formation of the trihydrochloride salt to afford the desired product (67 mg, 52%) as a green-brown solid: 1H NMR (500 MHz, CD3OD) δ 9.32 (s, 1H), 8.46 (d, J=9.0 Hz, 1H), 8.37 (d, J=9.0 Hz, 1H), 8.21 (d, J=2.5 Hz, 1H), 7.75 (dd, J=9.3, 2.5 Hz, 1H), 7.63-7.26 (m, 2H), 7.12 (d, J=9.3 Hz, 1H), 4.39 (d, J=10.5 Hz, 1H), 4.01-3.96 (m, 1H), 3.48-3.16 (m, 5H), 2.25-2.15 (m, 1H), 2.04-1.93 (m, 1H), 1.82-1.71 (m, 2H), 1.32-1.19 (m, 3H); ESI MS m/z 521 [M+H]+; HPLC>99% (AUC), tR=9.75 min.

Sources & evidence

ORD record
ord-f967d945f81f4ff6961e20037613858d
Source dataset
uspto-grants-2016_05
Patent number
US09345709B2

Reaction notes

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