Triethylamine → HCID 136121408, compound

HRID 2079419Notes

Reaction equation

HRID 2079419 reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:14])[O:8][C@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[CH2:2]1.Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[N:19]=[C:18]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[OH:33])[N:17]=1.C(N(CC)CC)C>C(Cl)Cl>[F:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[OH:33])[N:17]=[C:16]2[N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:14])[O:8][C@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 58010930HCID 58010930, compoundHCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

HCID 136121408HCID 136121408, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-tetrahydrofuran-3-yl (R)-pyrrolidin-3-ylcarbamate (225 mg, 1.12 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 in 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 (S)-tetrahydrofuran-3-yl (R)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (250 mg, 66%). LC/MS: m/z 439.5 (M+H)+ at 2.40 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J=7.8, 1.5 Hz, 1H), 7.99 (d, J=2.6 Hz, 1H), 7.87-7.91 (m, 1H), 7.74-7.79 (m, 1H), 7.70 (d, J=6.2 Hz, 1H), 7.35-7.39 (m, 1H), 6.91-6.96 (m, 2H), 5.15 (s, 1H), 4.21-4.25 (m, 2H), 4.12-4.14 (m, 1H), 4.01-4.06 (m, 1H), 3.87-3.89 (m, 1H), 3.65-3.78 (m, 4H), 2.02-2.26 (m, 3H), 1.82-1.89 (m, 1H) ppm.

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-431a6cc696a74541a676e4936176262d
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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