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

反応式

[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

参加物

反応物 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

生成物 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)methanone収率 67.7%

実験手順

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.

出典と根拠

ORDレコード: ord-a5b3b1bec64444069f0c95f6e9910d10
出典データセット: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US09345709B2

反応ノート

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