Dimethylformamide → HCID 178492072, compound

HRID 2376237Notes

Reaction equation

HRID 2376237 reaction equation
CN(C)C=O.[Cl:6][C:7]1[CH:8]=[C:9]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[N:17]=[C:16]([CH2:27][CH:28]([C:31]3[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=3)[C:29]#[N:30])[CH:15]=2)[CH:10]=[CH:11][C:12]=1[Cl:13].[Cl-].[NH4+].[N-:40]=[N+:41]=[N-:42].[Na+]>O.C(O)=O>[Cl:6][C:7]1[CH:8]=[C:9]([C:14]2[N:18]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:17]=[C:16]([CH2:27][CH:28]([C:29]3[NH:42][N:41]=[N:40][N:30]=3)[C:31]3[CH:32]=[C:33]([CH3:37])[CH:34]=[CH:35][CH:36]=3)[CH:15]=2)[CH:10]=[CH:11][C:12]=1[Cl:13]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 22171052HCID 22171052, compound

Product 1

HCID 178492072HCID 178492072, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a 48-mL pressure vessel (Chemglass) were added N,N-dimethylformamide (25.0 mL), 3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionitrile (2.76 g, 5.97 mmol, 1.0 equiv), ammonium chloride (1.58 g, 29.8 mmol, 5.0 equiv) and sodium azide (1.94 g, 29.8 mmol, 5.0 equiv). The screw-cap vessel was sealed and then placed in an oil bath heated to 90° C. for 48 h. The reaction mixture was cooled to room temperature, pH-adjusted with formic acid, diluted with water (100 mL), and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with water (3×50 mL) then brine (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude material was purified by flash chromatography (5% methanol/dichloromethane) to yield the title compound (1.9 g, 63%). HPLC: Rt=3.09 (Method A). MS (ESI): mass calculated for C26H22Cl2N6O, 504.12; m/z found, 505.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6): 7.57 (d, J=8.5 Hz, 1H), 7.41 (d, J=2.2 Hz, 1H), 7.23-7.16 (m, 3H), 7.09-7.07 (m, 3H), 7.01 (dd, J=8.5, 2.2 Hz, 1H), 6.96 (d, J=9.0 Hz, 2H), 6.46 (s, 1H), 4.86 (dd, J=9.0, 6.6 Hz, 1H), 3.77 (s, 3H), 3.62 (dd, J=14.8, 9.3 Hz, 1H), 3.35 (dd, J=14.8, 6.6 Hz, 1H), 2.28 (s, 3H).

Workup

  1. customThe screw-cap vessel was sealed
  2. customplaced in an oil bath
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined extracts were washed with water (3×50 mL)
  5. dry with materialbrine (50 mL), dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by flash chromatography (5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-90faf56fbdad472895eab72f903cce05
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

Loading…