3-(6,7-Dimethoxyquinazolin-4-ylthio)aniline → 1-(3-(2-Cyanopropan-2-yl)isoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl)urea

HRID 631747Notes

Reaction equation

HRID 631747 reaction equation
[C:1]([C:3]([C:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:20])OC2C=CC=CC=2)[O:8][N:7]=1)([CH3:5])[CH3:4])#[N:2].[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][C:32]=1[O:33][CH3:34])[N:29]=[CH:28][N:27]=[C:26]2[S:35][C:36]1[CH:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39]>C1COCC1>[C:1]([C:3]([C:6]1[CH:10]=[C:9]([NH:11][C:12]([NH:39][C:38]2[CH:40]=[CH:41][CH:42]=[C:36]([S:35][C:26]3[C:25]4[C:30](=[CH:31][C:32]([O:33][CH3:34])=[C:23]([O:22][CH3:21])[CH:24]=4)[N:29]=[CH:28][N:27]=3)[CH:37]=2)=[O:20])[O:8][N:7]=1)([CH3:4])[CH3:5])#[N:2]

Participants

4

Reactant 2

HCID 569536273-(6,7-Dimethoxyquinazolin-4-ylthio)anilineHCID 66877010Phenyl 3-(2-cyanopropan-2-yl)isoxazol-5-ylcarbamate

Product 1

HCID 582678241-(3-(2-Cyanopropan-2-yl)isoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl)ureaYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of phenyl 3-(2-cyanopropan-2-yl)isoxazol-5-ylcarbamate (prepared as described in Example 125A steps 1 through 3) (95 mg, 0.35 mmol), 3-(6,7-dimethoxyquinazolin-4-ylthio)aniline (prepared as described in Example 115B) (100 mg, 0.319 mmol) and N,N-4-(dimethylamino)pyridine (10 mg, 0.082 mmol) in THF (5 mL) was stirred at rt for 15 h. The reaction mixture was concentrated under reduced pressure to give the crude product which was partitioned between dichloromethane (10 mL) and water (10 mL). The organic layer was separated and dried over magnesium sulfate. Concentration under reduced pressure gave a solid which was triturated with methanol to afford 1-(3-(2-cyanopropan-2-yl) isoxazol-5-yl)-3-(3-(6,7-dimethoxyquinazolin-4-ylthio)phenyl)urea (50 mg, 32%) as a colorless solid. 1H NMR (300 MHz, DMSO-d6) δ10.52 (brs, 1H), 9.14 (brs, 1H), 8.70 (s, 1H), 7.86 (s, 1H), 7.57 (m, 1H), 7.46 (m, 1H), 7.30-7.36 (m, 3H), 6.28 (s, 1H), 3.99 (s, 6H), 1.68 (s, 6H); LC-MS (ESI) m/z 491 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give the crude product which
  3. customwas partitioned between dichloromethane (10 mL) and water (10 mL)
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. concentrationConcentration under reduced pressure
  7. customgave a solid which
  8. customwas triturated with methanol

Sources & evidence

ORD record
ord-1059ea2916824af28cebc608301d7a6b
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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