Binap, (A+-)- → 7-Chloro-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1970994Notes

Reaction equation

HRID 1970994 reaction equation
Cl[C:2]1[C:14]2[C:13]3[CH:12]=[CH:11][C:10]([Cl:15])=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:16]#[N:17])=[CH:4][N:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].[Cl-].[CH:71]1([C@@H:74]([NH3+:79])[C:75]([F:78])([F:77])[F:76])[CH2:73][CH2:72]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].COCCOC>[Cl:15][C:10]1[CH:11]=[CH:12][C:13]2[C:14]3[C:2]([NH:79][C@H:74]([CH:71]4[CH2:73][CH2:72]4)[C:75]([F:78])([F:77])[F:76])=[N:3][CH:4]=[C:5]([C:16]#[N:17])[C:6]=3[NH:7][C:8]=2[CH:9]=1

Participants

7

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 565950571,7-dichloro-5H-pyrido[4,3-b]indole-4-carbonitrileHCID 68669069(1R)-1-Cyclopropyl-2,2,2-trifluoroethanaminium chloride

Product 1

HCID 565954467-Chloro-1-{[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

1,7-Dichloro-5H-pyrido[4,3-b]indole-4-carbonitrile (5.0 g, 19 mmol), Pd2(dba)3 (0.873 g, 0.954 mmol), BINAP (1.782 g, 2.86 mmol), and sodium tert-butoxide (9.17 g, 95 mmol) were added to a flask. DME (125 ml) was added immediately followed by the addition of (1R)-1-cyclopropyl-2,2,2-trifluoroethanaminium chloride (5.02 g, 28.6 mmol). The reaction mixture was purged with nitrogen for 10 min, and heated at 85° C. overnight. The reaction was diluted with EtOAc, washed with water and brine, dried (magnesium sulfate), concentrated, and purified by flash chromatography to give the title compound. 1H NMR (600 MHz, CD3SOCD3) δ 12.63 (s, 1H); 8.56 (d, 1H); 8.40 (s, 1H); 7.54 (d, 1H); 7.47 (d, 1H); 7.36 (dd, 1H); 4.78 (m, 1H); 1.56 (m, 1H); 0.73 (m, 1H); 0.62 (m, 1H); 0.52 (m, 1H); 0.37 (m, 1H). LRMS (APCI) calc'd for (C17H12ClF3N4) [M+H]+, 365.1. found 365.0.

Workup

  1. customThe reaction mixture was purged with nitrogen for 10 min
  2. additionThe reaction was diluted with EtOAc
  3. washwashed with water and brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated
  6. custompurified by flash chromatography

Sources & evidence

ORD record
ord-7515bf84c46c4af6abdb48f24f5d4d79
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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