Trifluoroacetic acid → (R)-1-(4-((6-(3-aminopiperidin-1-yl)pyridin-3-yl)amino)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trihydrochloride

HRID 526234Notes

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])C[CH2:2]1.C(O)(C(F)(F)F)=O>>[ClH:43].[ClH:43].[ClH:43].[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](=[O:5])[CH2:1][CH3:2])=[CH:18][CH:19]=2)[CH2:24]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

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 137231126(R)-1-(4-((6-(3-aminopiperidin-1-yl)pyridin-3-yl)amino)-6-(3,5-dichloro-4-hydroxyphenyl)-1,5-naphthyridin-3-yl)propan-1-one trihydrochlorideYield 247.4%

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 (80 mg, 0.12 mmol) was reacted with TFA (2 mL) followed by formation of the trihydrochloride salt to afford the desired product (48 mg, 62%) as an orange solid: 1H NMR (500 MHz, CD3OD) δ 9.39 (s, 1H), 8.49 (d, J=9.5 Hz, 1H), 8.42 (d, J=9.0 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 7.92 (dd, J=9.5, 2.0 Hz, 1H), 7.58 (s, 2H), 7.28 (d, J=9.5 Hz, 1H), 4.42-4.32 (m, 1H), 4.16-3.96 (m, 1H), 3.52-3.22 (m, 5H), 2.29-2.18 (m, 1H), 2.08-1.98 (m, 1H), 1.88-1.75 (m, 2H), 1.37-1.20 (m, 3H); ESI MS m/z 537 [M+H]+; HPLC 98.0% (AUC), tR=9.92 min

Sources & evidence

ORD record: ord-ce0c595f452349c5b014c3e501a4ee74
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345709B2

Reaction notes

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