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 1918186Notes

Reaction equation

HRID 1918186 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) δ 10.52 (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-5cf42db18cb544f8b1de585a072181c0
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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