Triethylamine → tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

HRID 2062305Notes

Reaction equation

HRID 2062305 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:3]=1.[C:20]([O:24][C:25](=[O:32])[NH:26][C@@H:27]1[CH2:31][CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>CN(C=O)C.O.C(Cl)Cl>[OH:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:4]1[N:3]=[C:2]([N:29]2[CH2:30][CH2:31][C@@H:27]([NH:26][C:25](=[O:32])[O:24][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:28]2)[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121326tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamateYield 86%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 2-(4-chloro-7-methyl-quinazolin-2-yl)-phenol (644 mg, 2.4 mmol) in 2.9 mL of DMF at room temperature was added sequentially (R)— pyrrolidin-3-yl-carbamic acid tert-butyl ester (857 mg, 4.6 mmol) and triethylamine (662 μL, 4.8 mmol), and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with water (10 mL) and CH2Cl2 (10 mL). The organic layer was separated and dried (Na2SO4), and the residue was purified by silica gel chromatography with 25-85% ethyl acetate/hexanes to give tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (856 mg, 86%). LC/MS: m/z 421 (M+H)+ at 2.82 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried (Na2SO4)
  3. customthe residue was purified by silica gel chromatography with 25-85% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-d399fd2f12b74d95a661682320fe6078
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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