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 526134Notes

Reaction equation

[C:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1[NH:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]3[CH2:26][CH2:25][CH2:24][C@H:23]([NH:27]C(=O)OC(C)(C)C)[CH2:22]3)=[N:19][CH:20]=1)=[N:11][C:10]([C:35]1[CH:40]=[C:39]([F:41])[C:38]([OH:42])=[C:37]([Cl:43])[CH:36]=1)=[CH:9][CH:8]=2)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>>[ClH:43].[ClH:43].[ClH:43].[NH2:27][C@H:23]1[CH2:24][CH2:25][CH2:26][N:21]([C:18]2[N:19]=[CH:20][C:15]([NH:14][C:13]3[C:12]4[C:7](=[CH:8][CH:9]=[C:10]([C:35]5[CH:40]=[C:39]([F:41])[C:38]([OH:42])=[C:37]([Cl:43])[CH:36]=5)[N:11]=4)[N:6]=[CH:5][C:4]=3[C:1](=[O:3])[CH3:2])=[CH:16][CH:17]=2)[CH2:22]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-898929c80dd94c428b968da6de51984f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345709B2

Reaction notes

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