Boron tribromide → tert-Butyl 5-amino-2-methylthio-4-(3-hydroxyphenyl)-quinazoline-6-carboxamide

HRID 1766086Notes

Reaction equation

HRID 1766086 reaction equation
[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C)[CH:18]=3)=[N:10][C:11]([S:15][CH3:16])=[N:12]2)=[C:7]([NH2:25])[C:6]=1[C:26]([NH2:28])=[O:27])([CH3:4])([CH3:3])[CH3:2].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=3)=[N:10][C:11]([S:15][CH3:16])=[N:12]2)=[C:7]([NH2:25])[C:6]=1[C:26]([NH2:28])=[O:27])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 21109118tert-Butyl 5-amino-2-methylthio-4-(3-methoxyphenyl)-quinazoline-6-carboxamide

Product 1

HCID 21109116tert-Butyl 5-amino-2-methylthio-4-(3-hydroxyphenyl)-quinazoline-6-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of tert-butyl 5-amino-2-methylthio-4-(3-methoxyphenyl)-quinazoline-6-carboxamide (example 25f, 1.5 g) in dry CH2Cl2 was cooled to 0° C. A solution of BBr3 (1.1 ml) in CH2Cl2 (25 ml) was added dropwise and after the addition was complete, the mixture was stirred for 3 h at room temperature. The mixture was diluted with CH2Cl2 and a saturated aqueous NaHCO3 solution (200 ml) was carefully added. The mixture was vigorously stirred for 1.5 h until all solids dissolved. The aqueous layer was extracted twice with CH2Cl2. The first organic layer was washed with sat. aq. NaHCO3 and brine. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The title compound was purified by chromatography on silica gel with hept/EtOAc=1/0 to 1/1 (v/v) as eluent.

Workup

  1. additionafter the addition
  2. stirringThe mixture was vigorously stirred for 1.5 h until all solids
  3. dissolutiondissolved
  4. extractionThe aqueous layer was extracted twice with CH2Cl2
  5. washThe first organic layer was washed with sat. aq. NaHCO3 and brine
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe title compound was purified by chromatography on silica gel with hept/EtOAc=1/0 to 1/1 (v/v) as eluent

Sources & evidence

ORD record
ord-1bf173ea045e4e03b1001dbda9e4f86b
Source dataset
uspto-grants-2007_06
Patent number
US07229990B2

Reaction notes

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