1,2-Dibromopropane → (Z)-4-methyl-3-(2-propan-2-ylphenyl)-N-[(Z)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]-1,3-thiazolidin-2-imine

HRID 2409800Notes

Reaction equation

HRID 2409800 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([NH:13]/[N:14]=[CH:15]/[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=3)[N:23]=2)=[CH:18][CH:17]=1)=[S:12])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:45][CH:46](Br)[CH3:47]>CC(=O)CC.C(Cl)Cl>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH:46]([CH3:47])[CH2:45][S:12]/[C:11]/1=[N:13]/[N:14]=[CH:15]\[C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:28]=[CH:29][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:31][CH:32]=3)[N:23]=2)=[CH:20][CH:21]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 65531,2-DibromopropaneHCID 11430Potassium CarbonateHCID 885903141-(2-propan-2-ylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thiourea

Product 1

HCID 68157141(Z)-4-methyl-3-(2-propan-2-ylphenyl)-N-[(Z)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]-1,3-thiazolidin-2-imine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
85 °C

Procedure

To (E)-N-(2-isopropylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (300 mg, 0.572 mmol) and potassium carbonate (316 mg, 2.29 mmol) in butanone (4 ml) was added 1,2-dibromopropane (0.072 ml, 0.686 mmol). The reaction was heated to 85° C. overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided a yellow solid. The solid was recrystallized from MeOH. The solid was filtered, washed with MeOH, and dried to provide the title compound as a yellow solid which was dissolved in acetone and concentrated (3×). The light yellow solid was collected and dried under to provide the title compound as a 1:1 mixture of rotational diastereoisomers (75.1 mg, 0.133 mmol, 23%): mp 201-204° C.; 1H NMR of mixture (400 MHz, CDCl3) δ 8.56 (s, 2H), 8.18 (dd, J=10.8, 7.4 Hz, 6H), 7.84-7.73 (m, 8H), 7.45-7.30 (m, 8H), 7.30-7.23 (m, 2H), 7.20 (d, J=6.7 Hz, 1H), 7.12 (dd, J=7.8, 1.2 Hz, 1H), 4.43-4.33 (m, 1H), 4.16 (dd, J=12.6, 6.3 Hz, 1H), 3.48 (dt, J=13.3, 6.7 Hz, 1H), 3.37 (dd, J=10.8, 6.2 Hz, 1H), 3.24 (dt, J=13.7, 6.9 Hz, 1H), 3.08-2.92 (m, 3H), 1.33-1.16 (m, 18H); ESIMS m/z 566 (M+H).

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with DCM
  3. additionThe organic layers were poured through a phase separator
  4. concentrationconcentrated
  5. customPurification by flash column chromatography
  6. customprovided a yellow solid
  7. customThe solid was recrystallized from MeOH
  8. filtrationThe solid was filtered
  9. washwashed with MeOH
  10. customdried

Sources & evidence

ORD record
ord-c6d3d431cdb34ad1b53ecb7192485b6d
Source dataset
uspto-grants-2014_08
Patent number
US08815922B2

Reaction notes

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