Water → HCID 59361993, compound

HRID 1808474Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:14]2[N:23]=[C:22]([NH:24][C:25]3[CH:26]=[C:27]4[C:31](=[CH:32][CH:33]=3)[N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[N:29]=[CH:28]4)[C:21]3[C:16](=[CH:17][C:18]([O:42][CH3:43])=[C:19]([OH:41])[CH:20]=3)[N:15]=2)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Br[CH2:45][CH2:46][Cl:47].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:47][CH2:46][CH2:45][O:41][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][C:18]=1[O:42][CH3:43])[N:15]=[C:14]([C:4]1[CH:5]=[CH:6][C:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)=[C:2]([F:1])[CH:3]=1)[N:23]=[C:22]2[NH:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[N:29]=[CH:28]2

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of tert-butyl 5-(2-(3-fluoro-4-(phenyl)phenyl)-6-hydroxy-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.61 g, 1.06 mmol), 1-bromo-2-chloro ethane (0.475 g, 3.31 mmol) and K2CO3 (0.533 g, 3.86 mmol) in DMF (5 mL) was heated at 85° C. for 2.5 h. the mixture was allowed to cool to RT upon which, it was poured into water. A solid separated out which was collected via filtration and dried under vacuum. The residue was purified via preparative TLC (SiO2, CH2Cl2:MeOH 9:1) to give the desired compound tert-butyl 5-(6-(2-chloroethoxy)-2-(3-fluoro-4-(phenyl)phenyl)-7-methoxyquinazolin-4-ylamino)-1H-indazole-1-carboxylate (0.37 g, 0.578 mmol, 55%). MS 640.3 (M+1 Cl isotope pattern).

Workup

temperatureto cool to RT upon which, it
customA solid separated out which
filtrationwas collected via filtration
customdried under vacuum
customThe residue was purified via preparative TLC (SiO2, CH2Cl2:MeOH 9:1)

Sources & evidence

ORD record: ord-7ccfa992e5374367a26e8ca074ce7a39
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357693B2

Reaction notes

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