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 526226Notes

Reaction equation

[CH:1]1([C:4]([C:6]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[NH:16][C:17]2[CH:18]=[CH:19][C:20]([N:23]4[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29]C(=O)OC(C)(C)C)[CH2:24]4)=[N:21][CH:22]=2)=[N:13][C:12]([C:37]2[CH:42]=[C:41]([Cl:43])[C:40]([OH:44])=[C:39]([Cl:45])[CH:38]=2)=[CH:11][CH:10]=3)=[O:5])[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.FC(F)(F)C([O-])=O>>[NH2:29][C@@H:25]1[CH2:26][CH2:27][CH2:28][N:23]([C:20]2[N:21]=[CH:22][C:17]([NH:16][C:15]3[C:14]4[C:9](=[CH:10][CH:11]=[C:12]([C:37]5[CH:38]=[C:39]([Cl:45])[C:40]([OH:44])=[C:41]([Cl:43])[CH:42]=5)[N:13]=4)[N:8]=[CH:7][C:6]=3[C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])=[CH:18][CH:19]=2)[CH2:24]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-a5b3b1bec64444069f0c95f6e9910d10
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345709B2

Reaction notes

Loading…