Hydrochloric Acid → benzyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2062315Notes

Reaction equation

HRID 2062315 reaction equation
[CH2:1]([O:8][C:9](=[O:24])[NH:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.ClC1[C:36]2[C:31](=[CH:32][C:33]([CH3:37])=[CH:34][CH:35]=2)[N:30]=[C:29]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[OH:44])[N:28]=1.C(N(CC)CC)C>O1CCOCC1.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:24])[NH:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][N:14]([C:17]2[C:36]3[C:31](=[CH:32][C:33]([CH3:37])=[CH:34][CH:35]=3)[N:30]=[C:29]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[OH:44])[N:28]=2)[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 59254364(S)-tert-Butyl 3-((((benzyloxy)carbonyl)amino)methyl)pyrrolidine-1-carboxylateHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121473benzyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamateYield 68%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of benzyl((S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl)methylcarbamate (0.20 g, 0.60 mmol) and 4 M HCl in dioxane (10 mL) was stirred for 3 h at room temperature. After evaporating the solvent under reduced pressure, the solid was triturated with Et2O and dried under vacuum, then taken up in CH2Cl2 (10 mL). To this solution was added 2-(4-chloro-7-methylquinazolin-2-yl)phenol (0.16 g, 0.60 mmol) and triethylamine (0.25 mL, 1.8 mmol). The reaction mixture was stirred at room temperature overnight, then diluted with CH2Cl2 and washed with water. The organic extracts were dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 0-40% EtOAc in hexanes gave benzyl((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-yl)methylcarbamate as a colorless oil (0.19 g, 68%). LC/MS: m/z 469.1 (M+H)+ at 2.58 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customAfter evaporating the solvent under reduced pressure
  2. customthe solid was triturated with Et2O
  3. customdried under vacuum
  4. washwashed with water
  5. dry with materialThe organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-3c7539920e2b41b2953d35919940a893
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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