Trifluoroacetic acid → 1-(4-{[6-(3-Aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3-chloro-5-fluoro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)ethanone trihydrochloride
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][CH: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][CH: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]1Participants
3
Reactant 2
Product 1
Procedure
Following general procedure IV-2, 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 (33 mg, 33% over two steps) as an orange solid: 1H NMR (500 MHz, CD3OD) δ 9.38 (s, 1H), 8.48 (d, J=9.5 Hz, 1H), 8.41 (d, J=9.5 Hz), 8.25 (d, J=2.5 Hz, 1H), 7.91 (dd, J=9.5, 2.5 Hz, 1H), 7.41-7.37 (m, 2H), 7.28 (d, J=9.5 Hz, 1H), 4.37 (d, J=10.7 Hz, 1H), 4.03-3.99 (m, 1H), 3.52-3.32 (m, 3H), 2.84 (s, 3H), 2.28-2.20 (m, 1H), 2.08-1.98 (m, 1H), 1.84-1.78 (m, 2H); ESI MS m/z 507 [M+H]+; HPLC>99% (AUC), tR=9.38 min.
Sources & evidence
- ORD record
- ord-da5da30cde7f47c693b1ebb80dfd07b1
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09345709B2
Reaction notes
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