Trifluoroacetic acid → (R)-(4-{[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)(cyclopropyl)methanone

HRID 2178947Notes

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]([CH:42]3[CH2:44][CH2:43]3)=[O:41])=[CH:16][N:15]=2)[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.FC(F)(F)C([O-])=O>>[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]([CH:42]3[CH2:44][CH2:43]3)=[O:41])=[CH:18][CH:19]=2)[CH2:9]1

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 84468Trifluoroacetate

HCID 136981875(R)-tert-butyl [1-(5-{[3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-4-yl]amino}pyridin-2-yl)piperidin-3-yl]carbamate

Product 1

HCID 136266699(R)-(4-{[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino}-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)(cyclopropyl)methanoneYield 67.7%

Procedure

Following general procedure IV-2, (R)-tert-butyl[1-(5-{[3-(cyclopropanecarbonyl)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-4-yl}amino)pyridin-2-yl)piperidin-3-yl)carbamate (0.12 g, 0.18 mmol,) was reacted with TFA (2 mL). The resulting trifluoroacetate salt of the product was converted to the free base to afford the desired product (67 mg, 67%) as an orange solid: 1H NMR (500 MHz, CD3OD) δ 9.17 (s, 1H), 8.09 (d, J=9.0 Hz, 1H), 8.03 (d, J=9.0 Hz, 1H), 7.92 (d, J=2.5 Hz, 1H), 7.44 (s, 2H), 7.37 (dd, J=9.0, 2.5 Hz, 1H), 6.70 (d, J=9.0 Hz, 1H), 4.16-4.13 (m, 1H), 3.87-3.84 (m, 1H), 3.27-3.21 (m, 1H), 3.09-3.05 (m, 2H), 2.89-2.86 (m, 1H), 2.18-2.08 (m, 1H), 1.90-1.81 (m, 1H), 1.73-1.58 (m, 2H), 1.21-1.08 (m, 4H); ESI MS m/z 549 [M+H]+; HPLC>99% (AUC), tR=10.15 min.

Sources & evidence

ORD record: ord-a3156197bd524c83adfeb917257a5a65
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067937B2

Reaction notes

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