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

HRID 229634

Reaction equation

HRID 229634 reaction equation
C1COCC1.[NH2:6][C:7]1[C:12]2=[C:13]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][C:37]=4[F:46])=[O:34])=[CH:28][CH:27]=3)[C:14]([C:16]3[O:17][CH2:18][CH:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:20]=3)=[CH:15][N:11]2[N:10]=[CH:9][N:8]=1.C1CCN2C(=NCCC2)CC1.BrC(Cl)(Cl)Cl>C(Cl)Cl.CCOC(C)=O.CO.C(Cl)Cl>[NH2:6][C:7]1[C:12]2=[C:13]([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH:35][C:36]4[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][C:37]=4[F:46])=[O:34])=[CH:28][CH:27]=3)[C:14]([C:16]3[O:17][CH:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:20]=3)=[CH:15][N:11]2[N:10]=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 6383BromotrichloromethaneHCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57758258Ethyl 2-(4-amino-5-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-4,5-dihydro-1,3-oxazole-4-carboxylate

Product 1

HCID 57757975Ethyl 2-(4-amino-5-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-1,3-oxazole-4-carboxylateYield 65%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21901258Dichloromethane ethyl acetate methanolSolvent

Procedure

To a solution of THF (2 mL) and DCM (2 mL) cooled in an ice/water bath was added ethyl 2-(4-amino-5-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazin-6-yl)-4,5-dihydro-1,3-oxazole-4-carboxylate (Example 236) followed by DBU (24 μL, 0.16 mmol) and BrCCl3 (16 μL, 0.16 mmol). The solution was allowed to stir under N2 for 1 h and then the solution was left to warm to rt while stirring for 17 h. The reaction mixture was evaporated in vacuo and then purified by flash chromatography 50:45:5 v/v/v DCM/EtOAc/MeOH resulting in the isolation of 16 mg of the title compound as a white solid (0.028 mmol, yield 65%). 1H-NMR (DMSO-d6) δ 9.35 (s, 1H), 8.96 (d, J=2.8 Hz, 1H), 8.69 (s, 1H), 8.62 to 8.60 (d, J=9.3 Hz, 1H), 8.29 (s, 1H), 7.94 (s, 1H), 7.58 to 7.56 (d, J=8.4 Hz, 2H), 7.52 to 7.47 (m, 1H), 7.40 to 7.37 (m, 3H), 4.27 to 4.23 (q, J=6.3 Hz, 2H), 1.28 to 1.24 (t, J=7.1 Hz, 3H); MS [M+H]+=570.1; LCMS RT=3.16 min.

Workup

  1. waitthe solution was left
  2. stirringwhile stirring for 17 h
  3. customThe reaction mixture was evaporated in vacuo

Sources & evidence

ORD record
ord-ca5ecedf5bb94fbb974edb8d08775e1f
Source dataset
uspto-grants-2009_07
Patent number
US07563791B2

Linked notes

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