Morpholine → HCID 50938607, compound

HRID 1618566Notes

Reaction equation

HRID 1618566 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][CH:17]=[CH:18][C:19]=3[F:36])[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][CH:17]=[CH:18][C:19]=3[F:36])[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 86664277HCID 86664277, compound

Product 1

HCID 50938607HCID 50938607, 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)-5-fluoro-4-(6-iodo-3,3-dimethylindolin-1-yl)-3-methylquinoline (in a mixture with the 7-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)-5-fluoro-3-methylquinoline as a yellow oil. 1H NMR (400 MHz, chloroform-d) δ ppm 8.15 (2H, s), 8.00 (2H, t), 7.65 (1H, m), 7.28 (1H, m), 7.24 (1H, m), 7.17 (1H, m), 7.07 (1H, m), 3.62-3.95 (6H, m), 2.81-2.31 (4H, m), 2.35 (3H, s), 1.51 (3H, s), 1.45 (3H, s). Mass Spectrum (ESI) m/e=604 (M+1).

Workup

  1. customPrepared
  2. customPurification

Sources & evidence

ORD record
ord-225d9fa1403f49ed9114628c5b44964b
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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