N,N-Diethyl-2-propanamine → 3-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)urea

HRID 631635Notes

Reaction equation

HRID 631635 reaction equation
[F:1][C:2]([F:28])([C:7]1[CH:11]=[C:10]([NH:12][C:13](=O)[O:14]C2C=CC=CC=2)[N:9]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:8]=1)[C:3]([F:6])([F:5])[F:4].COC1C=C2C(=CC=1OC)N=C[N:35]=C2OC1C=C(C=CC=1)N.C(N(C(C)C)CC)C>C1COCC1>[F:28][C:2]([F:1])([C:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:14])[NH2:35])[N:9]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:8]=1)[C:3]([F:5])([F:6])[F:4]

Participants

5

Reactant 3

HCID 521913N,N-Diethyl-2-propanamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 86653532phenyl 3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-ylcarbamate

Product 1

HCID 1317354213-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)ureaYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A stirred mixture of phenyl 3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-ylcarbamate (199 mg, 0.50 mmol), 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (prepared as described in Example 113A) (100 mg, 0.34 mmol), N,N-diethylisopropylamine (88 mg, 0.68 mmol) in THF (1 mL) was heated at 60° C. for 15 h. After cooling to rt, the reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane. The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to afford the crude product. Purification via preparative HPLC afforded 14346,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(3-(perfluoroethyl)-1-phenyl-1H-pyrazol-5-yl)urea (80 mg, 39%) as a colorless solid. 1H NMR (400 MHz, DMSO-d6) 89.35 (s, 1H), 8.82 (s, 1H), 8.54 (s, 1H), 7.55-7.61 (m, 7H), 7.36-7.40 (m, 2H), 7.18 (m, 1H), 6.95 (m, 1H), 6.88 (s, 1H), 3.99 (s, 3H), 3.98 (s, 3H); LC-MS (ESI) m/z 601 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate solution and dichloromethane
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product
  7. customPurification via preparative HPLC

Sources & evidence

ORD record
ord-2254bda3cf7d431bbdee0136bc682bff
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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