Morpholine → HCID 50939345, compound

HRID 1618565Notes

Reaction equation

HRID 1618565 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([C:13]2[C:22]([CH3:23])=[C:21]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30](I)[CH:31]=4)[C:26]([CH3:35])([CH3:34])[CH2:25]3)[C:20]3[C:15](=[CH:16][C:17]([F:36])=[CH:18][CH:19]=3)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([C:13]2[C:22]([CH3:23])=[C:21]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([N:39]5[CH2:44][CH2:43][O:42][CH2:41][CH2:40]5)[CH:31]=4)[C:26]([CH3:35])([CH3:34])[CH2:25]3)[C:20]3[C:15](=[CH:16][C:17]([F:36])=[CH:18][CH:19]=3)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenylHCID 86664276HCID 86664276, compound

Product 1

HCID 50939345HCID 50939345, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Prepared according to procedure N using 2-(3,5-bis(trifluoromethyl)phenyl)-7-fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methylquinoline (in a mixture with the 5-F regioisomer; described herein) (160 mg, 0.25 mmol), morpholine (43 μL, 0.50 mmol), Pd2dba3 (34.1 mg, 0.037 mmol), 2-(dicyclohexylphosphino)-2,4,6-tri-i-propyl-1,1-biphenyl (35.5 mg, 0.074 mmol), and sodium tert-butoxide (71.6 mg, 0.745 mmol) in toluene (2.5 mL). The reaction was stirred at 105° C. for 1 h. Purification afforded 2-(3,5-bis(trifluoromethyl)phenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-7-fluoro-3-methylquinoline as a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 8.12 (2H, s), 8.00 (1H, s), 7.84-7.92 (1H, m), 7.80 (1H, ddd, J=9.5, 2.1, 1.0 Hz), 7.28-7.31 (1H, m), 7.10 (1H, dd, J=8.1, 1.1 Hz), 6.31-6.39 (1H, m), 5.57-5.64 (1H, m), 3.69-3.84 (6H, m), 2.93-3.00 (4H, m), 2.30 (3H, s), 1.53 (3H, s), 1.47 (3H, s). Mass Spectrum (ESI) m/e=604 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-09436cb6fb21477d97899cbce5127716
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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