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

HRID 1051728Notes

Reaction equation

HRID 1051728 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:18][C:17]([C:21]2[S:22][CH:23]=[C:24]([C:26]3[C:27]([O:41][CH:42]4[CH2:45][CH2:44][CH2:43]4)=[C:28]4[C:33](=[CH:34][CH:35]=3)[N:32]([C:36]([O:38][CH3:39])=[O:37])[C@@H:31]([CH3:40])[CH2:30][CH2:29]4)[N:25]=2)([O:19][CH3:20])[CH2:16]1)=O)(C)(C)C>ClCCl>[CH:42]1([O:41][C:27]2[C:26]([C:24]3[N:25]=[C:21]([C:17]4([O:19][CH3:20])[CH2:18][NH:15][CH2:16]4)[S:22][CH:23]=3)=[CH:35][CH:34]=[C:33]3[C:28]=2[CH2:29][CH2:30][C@H:31]([CH3:40])[N:32]3[C:36]([O:38][CH3:39])=[O:37])[CH2:43][CH2:44][CH2:45]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118076519(S)-methyl 6-(2-(1-(tert-butoxycarbonyl)-3-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118075875(S)-methyl 5-cyclobutoxy-6-(2-(3-methoxyazetidin-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-methoxyazetidin-3-yl)thiazol-4-yl)-5-cyclobutoxy-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.070 g, 0.13 mmol) in dichloromethane (3 mL), and the resulting solution stirred for 2 h at room temperature. The reaction mixture was concentrated under vacuum, and the residue was purified by preparative-HPLC with the following conditions (Waters I): Column, Xbridge C18, 5 um, 19×150 nm; Mobile phase water (0.05% ammonium bicarbonate) and acetonitrile (25% to 65% acetonitrile in 10 min; flow rate: 20 mL/min); Detector, 220&254 nm. This afforded (S)-methyl 5-cyclobutoxy-6-(2-(3-methoxyazetidin-3-yl)thiazol-4-yl)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.037 g, 65%) as an off-white solid. 1H NMR (400 MHz, CD3OD) 1.20 (d, J=6.80 Hz, 3H), 1.25-65 (m, 3H), 1.95-2.20 (m, 4H), 2.20-2.31 (m, 1H), 2.45-2.55 (m, 1H), 2.90-3.01 (m, 1H), 3.30 (s, 3H), 3.80 (s, 3H), 3.92-3.98 (m, 2H), 4.10-4.22 (m, 3H), 4.55-4.62 (m, 1H), 7.36 (d, J=8.40 Hz, 1H), 7.82 (d, J=8.40 Hz, 1H), 7.95 (s, 1H). MS (ESI, pos. ion) m/z 444 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customthe residue was purified by preparative-HPLC with the following conditions (Waters I)
  3. customMobile phase water (0.05% ammonium bicarbonate) and acetonitrile (25% to 65% acetonitrile in 10 min; flow rate: 20 mL/min)

Sources & evidence

ORD record
ord-c9d116ed2fdd404aa07cf293993d5808
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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