Bromotrichloromethane → Ethyl 2-(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-1,3-oxazole-4-carboxylate

HRID 229632

반응식

HRID 229632 반응식
[NH2:1][C:2]1[C:7]2=[C:8]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29]([NH:31][C:32]4[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=4)=[O:30])=[CH:24][CH:23]=3)[C:9]([C:11]([NH:13][C@H:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:15]O)=[O:12])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1.CCN(S(F)(F)F)CC.CC(C)=O.C(=O)=O.C1CCN2C(=NCCC2)CC1.BrC(Cl)(Cl)Cl>CCOC(C)=O.C1COCC1>[NH2:1][C:2]1[C:7]2=[C:8]([C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32]4[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=4)=[O:30])=[CH:26][CH:27]=3)[C:9]([C:11]3[O:12][CH:15]=[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[N:13]=3)=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1

참가 물질

8

반응물 5

HCID 6383Bromotrichloromethane2회HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2회HCID 123472(Diethylamino)sulfur trifluoride2회HCID 18522661Acetone cardiceHCID 68711530ethyl N-[(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)carbonyl]serinate

생성물 1

HCID 57758202Ethyl 2-(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-1,3-oxazole-4-carboxylate수율 8%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
-78 °C

실험 절차

To a solution of THF (16 mL) was added ethyl N-[(4-amino-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)carbonyl]serinate (Example 221) (437 mg, 0.76 mmol) which was cooled to −78° C. DAST (0.14 mL, 1.07 mmol) was added and the reaction proceeded for 1 h while stirring under N2. Additional DAST (0.14 mL, 1.07 mmol) was added and the solution was stirred for 30 min. The acetone/dry ice cooling bath was replaced with an ice/water bath and DBU (0.41 mL, 2.75 mmol) and BrCCl3 (0.27 mL, 2.75 mmol) were added and the solution was allowed to warm to rt over 17 h. Additional DBU (0.41 mL, 2.75 mmol) and BrCCl3 (0.27 mL, 2.75 mmol) were added and the solution was allowed to stir for 6 h. The reaction mixture was transferred to a separatory funnel, diluted with EtOAc (50 mL), washed with aq saturated NaHCO3 (50 mL) and H2O (50 mL). The aqueous fraction was back extracted with DCM (3×30 mL). The combined organic layers were dried (MgSO4), evaporated in vacuo and flashed 5:4:1 v/v/v DCM/EtOAc/MeOH resulting in the isolation of 33 mg of the title compound (0.060 mmol, yield 8%). 1H-NMR (DMSO-d6) δ 9.93 (s, 1H), 9.77 (s, 1H), 8.70 (s, 1H), 8.55 to 8.54 (d, J=5.0 Hz, 1H), 8.30 (s, 1H), 8.06 (s, 1H), 7.95 (s, 1H), 7.64 to 7.61 (d, J=8.8 Hz, 2H), 7.42 to 7.40 (d, J=8.8 Hz, 2H), 7.38 to 7.36 (d, J=6.2 Hz, 1H), 4.28 to 4.23 (q, J=7.6 Hz, 2H), 1.28 to 1.25 (t, J=7.1 Hz, 3H); MS [M+H]+=553.1; LCMS RT=3.04 min.

후처리

  1. stirringthe solution was stirred for 30 min
  2. temperatureto warm to rt over 17 h
  3. stirringto stir for 6 h
  4. customThe reaction mixture was transferred to a separatory funnel
  5. washwashed with aq saturated NaHCO3 (50 mL) and H2O (50 mL)
  6. extractionThe aqueous fraction was back extracted with DCM (3×30 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-040233e16b024647bb6f137cf015d880
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07563791B2

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