Cesium carbonate → {1-[2-(6,7-Dihydro-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalen-1-yl)-quinolin-8-yl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1745913노트

반응식

HRID 1745913 반응식
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([N:12]1[C:16]3=[CH:17][C:18]4[O:19][CH2:20][CH2:21][O:22][C:23]=4[CH:24]=[C:15]3[N:14]=[CH:13]1)[CH:8]=[CH:7]2.[C:25]([O:29][C:30](=[O:38])[NH:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)([CH3:28])([CH3:27])[CH3:26].C([O-])([O-])=O.[Cs+].[Cs+].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>O1CCOCC1.C(O)(C(F)(F)F)=O.C(Cl)Cl.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]>[C:25]([O:29][C:30](=[O:38])[NH:31][CH:32]1[CH2:37][CH2:36][N:35]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[C:9]([N:12]2[C:16]4=[CH:17][C:18]5[O:19][CH2:20][CH2:21][O:22][C:23]=5[CH:24]=[C:15]4[N:14]=[CH:13]2)[CH:8]=[CH:7]3)[CH2:34][CH2:33]1)([CH3:28])([CH3:26])[CH3:27]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 7238334-(N-Boc-amino)piperidineHCID 222269031-(8-Bromo-quinolin-2-yl)-6,7-dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalene

생성물 1

HCID 69559050{1-[2-(6,7-Dihydro-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalen-1-yl)-quinolin-8-yl]-piperidin-4-yl}-carbamic acid tert-butyl ester수율 54.5%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6344Dichloromethane용매HCID 6422Trifluoroacetic acid용매HCID 312751,4-Dioxane용매

실험 절차

1-(8-Bromo-quinolin-2-yl)-6,7-dihydro-1H-5,8-dioxa-1,3-diaza-cyclopenta[b]naphthalene 81C (700 mg, 1.83 mMol) and piperidin-4-yl-carbamic acid tert-butyl ester (733 mg, 3.66 mMol) were dissolved in 6.0 mL of dioxane under an atmosphere of dry N2. To this solution was added Cs2CO3 (835 mg, 2.56 mMol), racemic-BINAP (68 mg, 0.109 mMol) and tris(dibenzylideneacetone)dipalladium (0) (34 mg, 0.037 mMol) and the reaction mixture was heated to reflux and reacted at this temperature overnight. The mixture was then cooled to ambient temperature, filtered; and concentrated under vacuum to give 1.12 g of an orange film. The film was dissolved in a solution of 5 mL of TFA and 5 mL of DCM under an atmosphere of dry N2. The reaction mixture was stirred at ambient temperature for 30 minutes after which time it was concentrated under vacuum to give a yellow oil. The oil was partitioned between ethyl ether and 0.1 N aqueous HCl. The aqueous layer was then washed with DCM. The aqueous layer was basified to pH˜11 with NaOH. The resulting solution was washed three times with DCM. The DCM extracts were combined, dried over Na2SO4, filtered and concentrated to give 500 mg of a yellow solid. The solid was chromatographed on flash silica gel eluting with MeOH/DCM (1090) to give 127 mg of the title compound 81 as a yellow solid.

후처리

  1. temperatureto reflux
  2. customreacted at this temperature overnight
  3. filtrationfiltered
  4. concentrationand concentrated under vacuum
  5. customto give 1.12 g of an orange film
  6. concentrationwas concentrated under vacuum
  7. customto give a yellow oil
  8. customThe oil was partitioned between ethyl ether and 0.1 N aqueous HCl
  9. washThe aqueous layer was then washed with DCM
  10. washThe resulting solution was washed three times with DCM
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bd3751ee5cac41bd8ee2151391e89220
출처 데이터셋
uspto-grants-2006_03
특허 번호
US07019147B1

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