(R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine hydrochloride → (R)-3-hydroxy-1-methyl-2-oxo-N-(6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl)-1,2-dihydroquinoline-4-carboxamide

HRID 1844427Notes

Reaction equation

HRID 1844427 reaction equation
[OH:1][C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]2[C:10]([C:11]=1[C:12](Cl)=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2.[F:17][C:18]([F:30])([F:29])[C:19]1[CH:27]=[C:26]2[C:22]([CH2:23][CH2:24][C@H:25]2[NH2:28])=[CH:21][CH:20]=1.Cl.FC(F)(F)C1C=C2C(CC[C@H]2N)=CC=1>>[OH:1][C:2]1[C:3](=[O:16])[N:4]([CH3:15])[C:5]2[C:10]([C:11]=1[C:12]([NH:28][C@H:25]1[C:26]3[C:22](=[CH:21][CH:20]=[C:19]([C:18]([F:17])([F:29])[F:30])[CH:27]=3)[CH2:23][CH2:24]1)=[O:13])=[CH:9][CH:8]=[CH:7][CH:6]=2

Participants

4

Reactant 3

HCID 71743688(R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine hydrochlorideHCID 71743689(R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amineHCID 867310963-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-4-carbonyl chloride

Product 1

HCID 86731095(R)-3-hydroxy-1-methyl-2-oxo-N-(6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl)-1,2-dihydroquinoline-4-carboxamideYield 20%

Procedure

Following the procedure described for Example 3, Example 192 (4 mg, 9.94 μmol, 20% yield) was prepared as an off-white powder by using 3-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-4-carbonyl chloride (see Example 3C) and (R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-amine (Intermediate 15). LCMS=2.07 min, [M+1]=403.1 (Method A); Orthogonal HPLC (150×4.6 mm 3.5 μm, 254 nm): Sunfire {RT=9.47 min, 98%}; Xbridge {RT=8.63 min, 92%}. 1H NMR (500 MHz, MeOD) δ ppm 7.80 (1 H, s), 7.64 (1 H, d, J=8.3 Hz), 7.48-7.57 (3 H, m), 7.44 (1H, d, J=8.0 Hz), 7.31 (1 H, t, J=7.4 Hz), 5.76 (1 H, t, J=7.4 Hz), 3.81 (3 H, s), 3.08-3.18 (1 H, m), 2.98-3.06 (1 H, m), 2.67-2.74 (1 H, m), 2.05-2.13 (1 H, m).

Workup

  1. customwas prepared as an off-white powder
  2. customLCMS=2.07 min, [M+1]=403.1 (Method A)

Sources & evidence

ORD record
ord-edbf3977da4d4ae6b686a07f9bd34b95
Source dataset
uspto-grants-2015_02
Patent number
US08946430B2

Reaction notes

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