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

HRID 1618503Notes

Reaction equation

HRID 1618503 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[C:3]=1[CH3:19].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:31]=[C:30]3[NH:32][CH2:33][C:34]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[C:29]3=[CH:28][CH:27]=2)[CH2:22][CH2:21]1.Cl.O1CCOCC1>>[F:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:32]3[C:30]4[C:29](=[CH:28][CH:27]=[C:26]([N:23]5[CH2:22][CH2:21][O:20][CH2:25][CH2:24]5)[CH:31]=4)[C:34]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:33]3)=[C:3]([CH3:19])[C:4]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[N:5]2)=[CH:10][CH:9]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 672846616-Morpholino-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]HCID 672847364-Chloro-7-fluoro-3-methyl-2-(pyridin-4-yl)quinoline

Product 1

HCID 672847711-(7-Fluoro-3-methyl-2-(4-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-pyran]

Procedure

Prepare according to procedure L using 4-chloro-7-fluoro-3-methyl-2-(pyridin-4-yl)quinoline (60 mg, 220 μmol), 6-morpholino-2′,3′,5′,6′-tetrahydrospiro[indoline-3,4′-pyran] (60 mg, 220 μmol) and a 4.0M solution of HCl in 1,4-dioxane (0.05 mL, 0.22 mmol). After purification 1-(7-fluoro-3-methyl-2-(4-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran] was obtained as a yellow film. 1H NMR (500 MHz, chloroform-d) δ ppm 8.80 (2H, dd, J=4.3, 1.8 Hz), 7.74-7.92 (2H, m), 7.49-7.62 (2H, m), 7.25-7.32 (1H, m), 7.15 (1H, d, J=8.1 Hz), 6.36 (1H, dd, J=8.2, 2.3 Hz), 5.60 (1H, d, J=2.2 Hz), 4.01-4.08 (2H, m), 3.95 (2H, s), 3.74 (4H, t, J=5.1 Hz), 3.49-3.63 (2H, m), 2.90-3.03 (4H, m), 2.28 (3H, s), 2.10-2.22 (2H, m, J=14.2, 14.2, 12.0, 4.6 Hz), 1.85-1.93 (1H, m), 1.74-1.82 (1H, m). Mass Spectrum (ESI) m/e=511 (M+1).

Workup

  1. customPrepare
  2. customAfter purification 1-(7-fluoro-3-methyl-2-(4-pyridinyl)-4-quinolinyl)-6-(4-morpholinyl)-1,2,2′,3′,5′,6′-hexahydrospiro[indole-3,4′-pyran]
  3. customwas obtained as a yellow film

Sources & evidence

ORD record
ord-ba3061ff47f24900af6c987db066da84
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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