Diisopropylethylamine → 3-(5-(2-Methyl-1-morpholinopropan-2-yl)isoxazol-3-yl)urea

HRID 631628Notes

Reaction equation

HRID 631628 reaction equation
[CH3:1][C:2]([C:11]1[O:15][N:14]=[C:13]([NH:16][C:17](=[O:25])OC2C=CC=CC=2)[CH:12]=1)([CH3:10])[CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.C([N:29](CC)C(C)C)(C)C.COC1C=C2C(=CC=1OC)N=CN=C2OC1C=C(C=CC=1)N>C1COCC1>[CH3:1][C:2]([C:11]1[O:15][N:14]=[C:13]([NH:16][C:17](=[O:25])[NH2:29])[CH:12]=1)([CH3:10])[CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 498410023-[(6,7-Dimethoxy-4-quinazolinyl)oxy]anilineHCID 66876285Phenyl 5-(2-methyl-1-morpholinopropan-2-yl)isoxazol-3-ylcarbamate

Product 1

HCID 1317354203-(5-(2-Methyl-1-morpholinopropan-2-yl)isoxazol-3-yl)ureaYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of phenyl 5-(2-methyl-1-morpholinopropan-2-yl)isoxazol-3-ylcarbamate (22 mg), N,N-diisopropylethylamine (12 mg, 0.093 mmol) and 3-(6,7-dimethoxyquinazolin-4-yloxy)aniline (prepared as described in Example 113A) (15 mg, 0.051 mmol) in THF (0.5 mL) was heated at 60° C. for 15 h. The reaction mixture was cooled to rt and partitioned between saturated aqueous sodium carbonate and dichloromethane. The organic layer was separated and concentrated under reduced pressure to give the crude product. Purification via preparative TLC afforded 14346,7-dimethoxyquinazolin-4-yloxy)phenyl)-3-(5-(2-methyl-1-morpholinopropan-2-yl)isoxazol-3-yl)urea (5 mg, 1% over three steps) as a solid. 1H NMR (400 MHz, CDCl3) 89.35 (brs, 1H), 8.65 (brs, 2H), 7.66 (s, 1H), 7.57 (s, 1H), 7.29-7.41 (m, 3H), 7.01 (m, 1H), 6.10 (s, 1H), 4.09 (s, 6H), 3.63-3.66 (m, 4H), 2.40-2.70 (m, 6H), 1.32 (s, 6H); LC-MS (ESI) m/z 549 (M+H)+.

Workup

  1. custompartitioned between saturated aqueous sodium carbonate and dichloromethane
  2. customThe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customto give the crude product
  5. customPurification via preparative TLC

Sources & evidence

ORD record
ord-87cd899fd6374c079d1ef07f69b848f6
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

Loading…