Triethylamine → HCID 136121617, compound

HRID 2062296Notes

Reaction equation

HRID 2062296 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[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.[NH:20]1[CH2:25][CH2:24][CH:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:22][CH2:21]1.C(N(CC)CC)C>C(Cl)Cl>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[OH:19])[N:3]=[C:2]2[N:20]1[CH2:21][CH2:22][CH:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:24][CH2:25]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 1361214352-(4-Chloro-6-fluoroquinazolin-2-yl)phenol

Product 1

HCID 136121617HCID 136121617, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (0.20 g, 0.73 mmol) in CH2Cl2 (5 mL) was added dropwise a solution of tert-butyl piperidin-4-ylcarbamate (0.19 g, 0.95 mmol) and triethylamine (203 μL, 147 mg, 1.46 mmol) in CH2Cl2. The reaction was stirred for 3 h and then quenched with water. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated to obtain tert-butyl 1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)piperidin-4-ylcarbamate. The residue was dissolved in 10 mL CH2Cl2 and 3 mL TFA. The reaction was stirred for 2 hours and neutralized with a 1.0 M aqueous NaOH solution. The mixture was partitioned between H2O/CH2Cl2 and separated, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated to obtain 2-(4-(4-aminopiperidin-1-yl)-6-fluoroquinazolin-2-yl)phenol. LC/MS: m/z 339.3 (M+H)+ at 1.87 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA))

Workup

  1. customquenched with water
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3d3d64663cae48089b7f6fd425691d12
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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