Hydrochloric Acid → HCID 178483083, 화합물

HRID 1984903노트

반응식

HRID 1984903 반응식
C1OCCOCCOCCOCCOCCOC1.[Br:19][C:20]1[CH:25]=[CH:24][C:23](I)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1.[NH2:32][C@@H:33]1[CH2:38][CH2:37][C@H:36]([NH:39][C:40]2[N:49]=[C:48]([N:50]([CH2:53]C)[CH2:51]C)[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[N:41]=2)[CH2:35][CH2:34]1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[ClH:107]>CCOCC.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].C1COCC1>[ClH:107].[ClH:107].[Br:19][C:20]1[CH:25]=[CH:24][C:23]([NH:32][C@@H:33]2[CH2:34][CH2:35][C@H:36]([NH:39][C:40]3[N:49]=[C:48]([N:50]([CH3:53])[CH3:51])[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[N:41]=3)[CH2:37][CH2:38]2)=[C:22]([O:27][C:28]([F:31])([F:30])[F:29])[CH:21]=1

참가 물질

11

반응물 6

HCID 313Hydrochloric AcidHCID 2855718-Crown-6HCID 634876Binap, (A+-)-HCID 27364224-Bromo-2-(trifluoromethoxy)iodobenzeneHCID 23676156Sodium t-butoxideHCID 178463885HCID 178463885, 화합물

생성물 1

HCID 178483083HCID 178483083, 화합물수율 18%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a glass flask were added 18-crown-6 (647 mg, 2.45 mmol), 4-Bromo-1-iodo-2-trifluoromethoxy-benzene (770 mg, 2.10 mmol), cis-N2-(4-amino-cyclohexyl)-N4,N4-dimethyl-quinazoline-2,4-diamine obtained in step C of example 9 (500 mg, 1.75 mmol), sodium tert-butoxide (235 mg, 2.45 mmol), tris(dibenzylideneacetone)dipalladium (160 mg, 0.175 mmol), (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (160 mg, 0.175 mmol) and THF (3.5 mL). The reaction mixture was stirred at reflux 18 hr. The mixture was filtered through a pad of celite, concentrated, and purified by flash chromatography (NH-silica gel, 33% EtOAc in hexane) to give a pale yellow oil. To a solution of above oil in Et2O (2 mL) was added 4 M hydrogen chloride in EtOAc (0.3 mL). The mixture was stirred at ambient temperature for 30 min and concentrated. A solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min. The precipitate was collected by filtration, washed with Et2O, and dried under reduced pressure to give cis-N2-[4-(4-bromo-2-trifluoromethoxy-phenylamino)-cyclohexyl]-N4,N4-dimethyl-quinazoline-2,4-diamine dihydrochloride (189 mg, 18%) as a white solid.

후처리

  1. temperatureat reflux 18 hr
  2. filtrationThe mixture was filtered through a pad of celite
  3. concentrationconcentrated
  4. custompurified by flash chromatography (NH-silica gel, 33% EtOAc in hexane)
  5. customto give a pale yellow oil
  6. stirringThe mixture was stirred at ambient temperature for 30 min
  7. concentrationconcentrated
  8. stirringA solution of the residue in Et2O (2 mL) was stirred at ambient tempareture for 15 min
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with Et2O
  11. customdried under reduced pressure

출처 및 근거

ORD 기록
ord-163edc018bd04e6282360fe77f26dcbb
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07544690B2

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