Hydrochloric Acid → HCID 21104354, compound

HRID 1354101Notes

Reaction equation

HRID 1354101 reaction equation
Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][C:7]([CH2:15][CH2:16][CH3:17])([CH2:12][CH2:13][CH3:14])[C:6]=2[N:5]=[C:4]([CH3:18])[N:3]=1.[Cl:19][C:20]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:21]=1[NH2:22].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl.CCOCC>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:19][C:20]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:21]=1[NH:22][C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][C:7]([CH2:15][CH2:16][CH3:17])([CH2:12][CH2:13][CH3:14])[C:6]=2[N:5]=[C:4]([CH3:18])[N:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 111232,4-DichloroanilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 21104381HCID 21104381, compound

Product 1

HCID 21104354HCID 21104354, compoundYield 84.3%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Chloro-2-methyl-8,8-dipropyl-5,6,7,8-tetrahydroquinazoline (114 mg, 0.42 mmol), 2,4-dichloroaniline (76 mg, 0.47 mmol), and 4-toluenesulfonic acid hydrate (203 mg, 1.06 mmol) were combined in toluene (4 mL) and heated in an oil bath at 100° for 28 hrs. The mixture was cooled to room temp, diluted with EtOAc (30 mL), washed with sat. NaHCO3 solution, brine and dried over MgSO4. Evaporation afforded 262 mg of crude product which was purified by flash chromatography and eluted with CH2Cl2:hexane (1:1). This afforded 151 mg (90%) as a viscous liquid which crystallized on standing. This material was dissolved in EtOAc (1.5 mL) and then treated all at once with 2N HCl in Et2O (0.40 mL, 2 eq). The resulting white solid was filtered off, washed with a little Et2O and dried to afford 139 mg of (2,4-dichlorophenyl)-(2-methyl-8,8-dipropyl-5,6,7,8-tetrahydroquinazolin-4-yl)amine as a hydrochloride salt. Mp 238.3°−243.9° C. MS (ES+) 392 (M+H).

Workup

  1. temperatureheated in an oil bath at 100° for 28 hrs
  2. washwashed with sat. NaHCO3 solution, brine
  3. dry with materialdried over MgSO4
  4. customEvaporation
  5. customafforded 262 mg of crude product which
  6. customwas purified by flash chromatography
  7. washeluted with CH2Cl2:hexane (1:1)
  8. customThis afforded 151 mg (90%) as a viscous liquid which crystallized
  9. dissolutionThis material was dissolved in EtOAc (1.5 mL)
  10. filtrationThe resulting white solid was filtered off
  11. washwashed with a little Et2O
  12. customdried

Sources & evidence

ORD record
ord-c875cbf3c25d4db5bff840f30d2c2ec1
Source dataset
uspto-grants-2007_05
Patent number
US07223767B2

Reaction notes

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