Triethylamine → HCID 136201228, compound

HRID 1693017Notes

Reaction equation

HRID 1693017 reaction equation
C(O)(=O)C(O)=O.[NH:7]1[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8]1.Cl[C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:34])[CH:32]=2)[N:27]=[C:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[OH:41])[N:25]=1.C(N(CC)CC)C>C(Cl)Cl>[F:34][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]=[C:26]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[OH:41])[N:25]=[C:24]2[N:7]1[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:8]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 86621293Carbamic acid, (3R)-3-pyrrolidinyl-, phenylmethyl ester, ethanedioate (1:1)HCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

HCID 136201228HCID 136201228, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (R)-benzyl pyrrolidin-3-ylcarbamate oxalate (1.35 g, 4.38 mmol) in CH2Cl2 (5 mL) was added dropwise to a solution of 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (1.0 g, 3.6 mmol) and triethylamine (1.22 mL, 8.76 mmol) in CH2Cl2 (10 mL). After stirring the mixture for 2 h, the reaction was quenched with H2O, the layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was purified via silica gel chromatography using 5-10% EtOAc in CH2Cl2 to give (R)-benzyl 1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (1.37 g, 82%). 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=6.9 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J=8.5 Hz, 1H), 7.46 (m, 1H), 7.37 (m, 6H), 7.01 (d, J=7.8 Hz, 1H), 6.90 (t, J=7.5 Hz, 1H), 5.17 (m, 2H), 4.51 (s, 1H), 4.25 (m, 1H), 4.10 (m, 2H), 3.91 (m, 1H), 2.37 (m, 1H), 2.12 (m, 1H). LC/MS: m/z 459.5 (M+H)+ at 2.80 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customthe reaction was quenched with H2O
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with CH2Cl2
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-20a5ba7901524b9591965f812679e22d
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

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