Triethylamine → HCID 136121331, compound

HRID 2062331Notes

Reaction equation

HRID 2062331 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([CH:9]2[CH2:11][CH2:10]2)=[O:8])[CH2:2]1.Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([F:23])[CH:21]=2)[N:16]=[C:15]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[OH:30])[N:14]=1.C(N(CC)CC)C>C(Cl)Cl>[F:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[N:16]=[C:15]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[OH:30])[N:14]=[C:13]2[N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([CH:9]2[CH2:10][CH2:11]2)=[O:8])[CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 58683903HCID 58683903, compoundHCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

HCID 136121331HCID 136121331, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of N-((R)-pyrrolidin-3-yl)cyclopropanecarboxamide (250 mg, 0.86 mmol), 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (250 mg, 0.86 mmol) and triethylamine (0.240 mL, 1.72 mmol) in CH2Cl2 (10 mL) was stirred at room temperature. The reaction was complete after one hour. The reaction was quenched with water, the aqueous layer was extracted twice with CH2Cl2, and the combined organic extracts were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc/CH2Cl2 gave N-((R)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-yl)cyclopropanecarboxamide (230 mg, 68%). LC/MS: m/z 393.3 (M+H)+ at 2.35 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.42-8.46 (m, 2H), 8.03 (dd, J=10.5, 2.6 Hz, 1H), 7.88-7.92 (m, 1H), 7.74-7.79 (m, 1H), 7.35-7.39 (m, 1H), 6.92-6.96 (m, 2H), 4.44-4.47 (m, 1H), 4.01-4.28 (m, 3H), 3.83-3.87 (m, 1H), 2.20-2.28 (m, 1H), 1.99-2.06 (m, 1H), 1.51-1.57 (m, 1H), 0.63-0.73 (m, 4H).

Workup

  1. customThe reaction was quenched with water
  2. extractionthe aqueous layer was extracted twice with CH2Cl2
  3. dry with materialthe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-3416f94b60634d15bd91f0f95d869dc0
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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