Binap, (A+-)- → 7-Chloro-1-{[(7R,8R)-7-methyl-1,4-dioxaspiro[4.5]dec-8-yl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1971007Notes

Reaction equation

HRID 1971007 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([O-])(C)C.[Na+].[CH3:70][C@H:71]1[C@H:80]([NH2:81])[CH2:79][CH2:78][C:73]2([O:77][CH2:76][CH2:75][O:74]2)[CH2:72]1>CCOC(C)=O.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:81][C@@H:80]4[CH2:79][CH2:78][C:73]5([O:74][CH2:75][CH2:76][O:77]5)[CH2:72][C@H:71]4[CH3:70])=[N:3][CH:4]=[C:5]([C:16]#[N:17])[C:6]=3[NH:7][C:8]=2[CH:9]=1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 565950571,7-dichloro-5H-pyrido[4,3-b]indole-4-carbonitrileHCID 59543149(7R,8R)-7-Methyl-1,4-dioxaspiro[4.5]decan-8-amine

Product 1

HCID 686692527-Chloro-1-{[(7R,8R)-7-methyl-1,4-dioxaspiro[4.5]dec-8-yl]amino}-5H-pyrido[4,3-b]indole-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A flask containing 1,7-dichloro-5H-pyrido[4,3-b]indole-4-carbonitrile (Example 1 Step 4, 140 mg, 0.53 mmol), BINAP (50 mg, 0.08 mmol), Pd2(dba)3 (24 mg, 0.03 mmol), and NaOtBu (164 mg, 1.71 mmol) was evacuated and refilled with nitrogen (×3). Degassed DME (10 mL) and (7R,8R)-7-methyl-1,4-dioxaspiro[4.5]decan-8-amine (183 mg, 1.07 mmol) were added to the mixture. The reaction mixture was heated to 85° C. overnight, cooled to room temperature, diluted with EtOAc, and washed with water and brine. The organic layer was dried (sodium sulfate), concentrated, and purified by flash chromatography to afford the title compound. LRMS (APCI) calc'd for (C21H21ClN4O2) [M+H]+, 397.1. found 397.0.

Workup

  1. customwas evacuated
  2. additionrefilled with nitrogen (×3)
  3. temperaturecooled to room temperature
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried (sodium sulfate)
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-685499e26cfa407c87364e0b8faabfc1
Source dataset
uspto-grants-2013_04
Patent number
US08431569B2

Reaction notes

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