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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 1971007
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HRID 1971007 반응식
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
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참가 물질

8

반응물 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

생성물 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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 80711,2-Dimethoxyethane용매HCID 8857Ethyl Acetate용매

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온도
85 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-685499e26cfa407c87364e0b8faabfc1
출처 데이터셋
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08431569B2

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