Trifluoroacetic acid → (S)-methyl 5-cyclobutoxy-6-(2-(3-fluoroazetidin-3-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051726Notes

Reaction equation

HRID 1051726 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:18][C:17]([C:20]2[S:21][CH:22]=[C:23]([C:25]3[C:26]([O:40][CH:41]4[CH2:44][CH2:43][CH2:42]4)=[C:27]4[C:32](=[CH:33][CH:34]=3)[N:31]([C:35]([O:37][CH3:38])=[O:36])[C@@H:30]([CH3:39])[CH2:29][CH2:28]4)[N:24]=2)([F:19])[CH2:16]1)=O)(C)(C)C>ClCCl>[CH:41]1([O:40][C:26]2[C:25]([C:23]3[N:24]=[C:20]([C:17]4([F:19])[CH2:18][NH:15][CH2:16]4)[S:21][CH:22]=3)=[CH:34][CH:33]=[C:32]3[C:27]=2[CH2:28][CH2:29][C@H:30]([CH3:39])[N:31]3[C:35]([O:37][CH3:38])=[O:36])[CH2:42][CH2:43][CH2:44]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118075426(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-fluoro azetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118075891(S)-methyl 5-cyclobutoxy-6-(2-(3-fluoroazetidin-3-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 mL) was added to a solution of (S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-fluoro azetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.059 g, 0.11 mmol) in dichloromethane (3 mL), and the resulting solution stirred for 2 h at room temperature and was then concentrated under vacuum. The residue was purified by preparative-HPLC with the following conditions (Waters I): Column, XBridge C18, 19×150 mm, 5 um; Mobile phase: water (0.05% ammonium bicarbonate) and acetonitrile (5% to 95% acetonitrile in 8 min; flow rate: 20 mL/min); Detector, UV 220&254 nm. This afforded (S)-methyl 5-cyclobutoxy-6-(2-(3-fluoro azetidin-3-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.025 g, 53%) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.20 (d, J=6.40 Hz, 3H), 1.31-1.40 (m, 1H), 1.45-1.55 (m, 1H), 1.55-1.66 (m, 1H), 2.02-2.18 (m, 4H), 2.22-2.31 (m, 1H), 2.49-2.55 (m, 1H), 2.95-3.06 (m, 1H), 3.80 (s, 3H), 4.08-4.20 (m, 3H), 4.28-4.36 (m, 2H), 4.56-4.64 (m, 1H), 7.24-7.27 (m, 1H), 7.67-7.73 (m, 2H). MS (ESI, pos. ion) m/z 432 [M+H]+.

Workup

  1. concentrationwas then concentrated under vacuum
  2. customThe residue was purified by preparative-HPLC with the following conditions (Waters I)
  3. customwater (0.05% ammonium bicarbonate) and acetonitrile (5% to 95% acetonitrile in 8 min; flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-dce42071549f43e189570efefc07327e
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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