Hydrochloric Acid → 1-(7-Fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

HRID 1618543Notes

Reaction equation

HRID 1618543 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]3[NH:13][CH2:14][C:15]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:10]3=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=2)[N:25]=[C:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[S:39]([CH3:42])(=[O:41])=[O:40])[C:23]=1[CH3:43].Cl.O1CCOCC1>CN1C(=O)CCC1>[F:32][C:28]1[CH:27]=[C:26]2[C:31]([C:22]([N:13]3[C:11]4[C:10](=[CH:9][CH:8]=[C:7]([N:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)[CH:12]=4)[C:15]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH2:14]3)=[C:23]([CH3:43])[C:24]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[S:39]([CH3:42])(=[O:40])=[O:41])=[N:25]2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 672846274-Chloro-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinolineHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]

Product 1

HCID 509394751-(7-Fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Prepared according to procedure L using 6-morpholino-2′,3′,5′,6′-tetrahydrospiro-[indoline-3,4′-pyran] (76 mg, 0.28 mmol) (described herein), 4-chloro-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (97 mg, 0.28 mmol) (described herein), 4.0 M hydrochloric acid in 1,4-dioxane (0.07 mL, 0.28 mmol), and NMP (0.476 mL). After purification 1-(7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran] was obtained as an orange solid. Compound is rotameric. 1H NMR (400 MHz, chloroform-d) δ ppm 8.16-8.30 (1H, m), 7.90 and 8.00 (1H, m), 7.75-7.85 (1H, m), 7.63-7.75 (2H, m), 7.42-7.53 (1H, m), 7.28-7.39 (1H, m), 7.06-7.18 (1H, m), 6.25-6.40 (1H, m), 5.65 and 5.81 (1H, m), 4.21 (1H, m), 3.85-4.09 (3H, m), 3.69-3.83 (5H, m), 3.63 (1H, m), 3.46-3.59 (1H, m), 3.16 (1H, s), 2.91-3.13 (6H, m), 2.09-2.24 (2H, m), 1.95 (2H, m), 1.89 (1H, m), 1.66-1.79 (1H, m). Mass Spectrum (ESI) m/e=588 (M+1).

Workup

  1. customPrepared
  2. customAfter purification 1-(7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]
  3. customwas obtained as an orange solid

Sources & evidence

ORD record
ord-72579496b6cb4b519fe32381e43f3acd
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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