1,2-Dichloroethane → HCID 46215630, compound

HRID 62545Notes

Reaction equation

HRID 62545 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=2[C:21](O)=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1.C1C=CC2[N:37]([OH:38])N=NC=2C=1.[CH2:39](Cl)CCl.CCN(C(C)C)C(C)C>CN(C)C=O.C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:22])=[CH:4][C:5]([NH:8][C:9]2[N:13]([CH:14]([CH3:15])[CH3:16])[N:12]=[C:11]([CH3:17])[CH:10]=2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667696182-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid

Product 1

HCID 46215630HCID 46215630, compoundYield 35.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluorobenzoic acid (2.5 g, 6.19 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added HOBT (1.138 g, 7.43 mmol) and EDC (1.424 g, 7.43 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (0.620 g, 7.43 mmol) and after 30 min the mixture was cooled to 0° C. Then DIEA (3.23 mL, 18.57 mmol) was added. The reaction mixture was stirred at the room temperature for 24 hr. Water (100 mL) followed by acetic acid (1 mL) were added and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and condensed. The resulting oil was purified by flash column chromatography on silica gel (2:1 DCM: EtOAc). 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-4-fluoro-N-(methyloxy)benzamide (1 g, 2.195 mmol, 35.5% yield) was isolated as a yellow foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.28 (d, J=6.57 Hz, 6 H) 2.11 (s, 3 H) 3.71 (s, 3 H) 4.41 (quin, J=6.51 Hz, 1 H) 5.97 (s, 1 H) 6.74 (s, 1 H) 6.87-7.06 (m, 1 H) 7.39 (dd, J=11.37, 2.53 Hz, 1 H) 7.66 (dd, J=8.46, 6.69 Hz, 1 H) 8.03 (s, 1 H) 8.57 (s, 1 H) 9.96 (br. s., 1 H) 11.98 (br. s., 1 H); HPLC Rt=2.36 min, MS (ESI): 433.3 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at the room temperature for 24 hr
  2. additionwere added
  3. extractionthe solution extracted with 2×50 ml of ethyl acetate
  4. washThe organic layer was washed with 2×50 ml
  5. dry with materialdried over MgSO4 and condensed
  6. customThe resulting oil was purified by flash column chromatography on silica gel (2:1 DCM: EtOAc)

Sources & evidence

ORD record
ord-c5db5b44a408477ab7f40be9a80adc78
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

Loading…