Hydrochloric Acid → 1-(4-(6-(3-Aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)propan-1-one

HRID 2271854Notes

Reaction equation

HRID 2271854 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]=[CH:15][C:14]([C:20](=[O:23])[CH2:21][CH3:22])=[C:13]3[NH:24][C:25]2[CH:26]=[CH:27][C:28]([N:31]3[CH2:36][CH2:35][CH2:34][CH:33]([NH:37]C(=O)OC(C)(C)C)[CH2:32]3)=[N:29][CH:30]=2)[CH:5]=[C:6]([F:9])[C:7]=1[OH:8].Cl>ClCCl.C(OCC)C>[NH2:37][CH:33]1[CH2:34][CH2:35][CH2:36][N:31]([C:28]2[N:29]=[CH:30][C:25]([NH:24][C:13]3[C:12]4[C:17](=[CH:18][CH:19]=[C:10]([C:4]5[CH:5]=[C:6]([F:9])[C:7]([OH:8])=[C:2]([Cl:1])[CH:3]=5)[CH:11]=4)[N:16]=[CH:15][C:14]=3[C:20](=[O:23])[CH2:21][CH3:22])=[CH:26][CH:27]=2)[CH2:32]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66716421Tert-butyl 1-(5-(6-(3-chloro-5-fluoro-4-hydroxyphenyl)-3-propionylquinolin-4-ylamino)pyridin-2-yl)piperidin-3-ylcarbamate

Product 1

HCID 566407281-(4-(6-(3-Aminopiperidin-1-yl)pyridin-3-ylamino)-6-(3-chloro-5-fluoro-4-hydroxyphenyl)quinolin-3-yl)propan-1-oneYield 60.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

tert-butyl 1-(5-(6-(3-chloro-5-fluoro-4-hydroxyphenyl)-3-propionylquinolin-4-ylamino)pyridin-2-yl)piperidin-3-ylcarbamate (32 mg, 0.051 mmol) was dissolved in dichloromethane (5 mL). To this solution was added a 2.0 M HCl solution in diethyl ether (2 mL) the mixture was stirred for 16 h at room temperature where a precipitate formed. The precipitate was filtered off, washed with dichloromethane (10 mL), dried under vacuum to obtain the desired product as the HCl salt (16 mg, 49%) as an orange solid: 1H NMR (500 MHz, MeOD) δ 9.28 (s, 1H), 8.23 (m, 2H), 8.01 (m, 2H), 7.75 (d, J=8.5 Hz, 1H), 7.19 (d, J=8.4 Hz, 1H), 7.10 (t, J=4.9 Hz, 2H), 4.54 (s, 1H), 4.04 (d, J=13.0 Hz, 1H), 3.36 (m, 3H), 3.24 (q, J=13.3, 6.2 Hz, 1H), 2.20 (m, 1H), 1.97 (m, 1H), 1.74 (m, 2H), 1.26 (t, J=6.6 Hz, 3H); ESI MS m/z 520, [C28H27ClFN5O2+H]+; HPLC 98.7% (AUC), tR=10.05 min.

Workup

  1. customformed
  2. filtrationThe precipitate was filtered off
  3. washwashed with dichloromethane (10 mL)
  4. customdried under vacuum

Sources & evidence

ORD record
ord-63e6aa0fbc3d4678be0a7955cb11932d
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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