Water → HCID 136068468, compound

HRID 2189236Notes

Reaction equation

HRID 2189236 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([OH:31])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C@H:19]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CC(N(C)C)=O>[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:2]2[CH:3]=[CH:4][C:5]([OH:31])=[C:6]([C:8]3[N:17]=[C:16]([NH:18][C@H:19]4[CH2:23][CH2:22][NH:21][CH2:20]4)[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[N:9]=3)[CH:7]=2)=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 136068483HCID 136068483, compound

Product 1

HCID 136068468HCID 136068468, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

(S)-tert-Butyl 3-(2-(5-bromo-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1-carboxylate (0.051 g, 0.105 mmol, prepared in a method analogous to that described in Synthesis 2-A), 4-fluorobenzene boronic acid (0.016 g, 0.114 mmol), palladium tetrakistriphenyl phosphine (0.028 g, 0.024 mmol) and potassium phosphate (0.051 g, 0.243 mmol) were dissolved in dimethyl acetamide (0.7 mL) and water (0.3 mL) and the mixture was heated in a microwave for 10 mins at 150° C. The mixture was filtered through a short plug of silica using ethyl acetate as eluent and the filtrate concentrated in vacuo. The residue was dissolved in methanol (1.2 mL) and 4M HCl in dioxane (1.2 mL) was added and the mixture stirred for 16 h. The mixture was concentrated and purified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g), eluting with methanol and then 1 M ammonia in methanol. The basic fractions were combined and purified by silica column chromatography, eluting with dichloromethane then 10% methanol in dichloromethane, to give the title compound as a yellow solid (0.013 g, 27%).

Workup

  1. filtrationThe mixture was filtered through a short plug of silica
  2. concentrationthe filtrate concentrated in vacuo
  3. dissolutionThe residue was dissolved in methanol (1.2 mL)
  4. addition4M HCl in dioxane (1.2 mL) was added
  5. concentrationThe mixture was concentrated
  6. custompurified by ion exchange chromatography on SCX-2 Isolute acidic resin (2 g)
  7. washeluting with methanol
  8. custompurified by silica column chromatography
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-6c03dd40de1f423889a9eb1dc4a37992
Source dataset
uspto-grants-2012_12
Patent number
US08324226B2

Reaction notes

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