4-(Trifluoromethyl)phenyl isocyanate → HCID 58770728, compound

HRID 657226Notes

Reaction equation

HRID 657226 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.[N:21]([C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)=[C:22]=[O:23]>CN(C=O)C>[F:31][C:30]([F:32])([F:33])[C:27]1[CH:26]=[CH:25][C:24]([NH:21][C:22]([N:18]2[CH2:19][CH2:20][CH:15]([C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[N:9]=[CH:8][N:7]=3)[CH2:16][CH2:17]2)=[O:23])=[CH:29][CH:28]=1

Participants

4

Reactant 2

HCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 595517346,7-Dimethoxy-4-(piperidin-4-yl)quinazoline

Product 1

HCID 58770728HCID 58770728, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6,7-dimethoxy-4-piperidin-4-yl-quinazoline (20 mg, 0.0733 mmol), as prepared in Example 1d, in DMF (1 mL) was treated with 1-isocyanato-4-trifluoromethyl-benzene (20 mg, 0.107 mmol) at RT overnight. The reaction was then partitioned between EtOAc (10 mL) and H2O (10 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. Purification by prep tlc (1:9 MeOH/DCM) afforded the title compound as a yellow solid (9.0 mg, 27%). 1H NMR (300 MHz, CDCl3) δ 9.10 (s, 1H), 7.54 (m, 2H), 7.39 (m, 1H), 7.28 (m, 2H), 6.69 (m, 1H), 6.63 (br s, NH), 4.33-4.29 (m, 2H), 4.09 (s, 6H), 3.65 (m, 1H), 3.22 (m, 2H), 2.17 (m, 2H), 2.06-2.01 (m, 2H); LC/MS (ESI) calcd mass 460.2, found 461.3 [M+1]+.

Workup

  1. customThe reaction was then partitioned between EtOAc (10 mL) and H2O (10 mL)
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customPurification by prep tlc (1:9 MeOH/DCM)

Sources & evidence

ORD record
ord-cc6c6ab50c6443949c238d0eaceaca52
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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