1,2-Dichloroethane → HCID 46215627, compound

HRID 62532Notes

Reaction equation

HRID 62532 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)[CH:3]=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[CH:10]=[CH:9][C:5]([C:6]([NH:37][O:38][CH3:39])=[O:8])=[C:4]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:19][C:20]3[N:24]([CH:25]([CH3:27])[CH3:26])[N:23]=[C:22]([CH3:28])[CH:21]=3)[CH:13]=2)[CH:3]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667692534-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid

Product 1

HCID 46215627HCID 46215627, compoundYield 29.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of 4-chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]benzoic acid (260 mg, 0.619 mmol) in N,N-dimethylformamide (DMF) (20 mL) was added HOBT (114 mg, 0.742 mmol) and EDC (142 mg, 0.742 mmol) and the reaction mixture was stirred for 30 min. To this solution was added O-methoxylamine hydrochloride (62.0 mg, 0.742 mmol), and after 30 min the reaction was cooled to 0° C. and DIEA (0.323 mL, 1.856 mmol) was added. The reaction mixture was stirred at the room temperature over the weekend. Water (100 mL) followed by acetic acid (1 mL) were added and the reaction mixture was extracted with 2×50 ml of ethyl acetate. The organic layer was washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The resulting yellow oil was purified by flash column chromatography on silica gel using DCM:EtOAc (10% to 100%). 4-Chloro-2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-N-(methyloxy)benzamide (85 mg, 0.180 mmol, 29.1% yield) was isolated as white foam. 1H NMR (400 MHz, DMSO-d6) ppm 1.27 (d, J=6.57 Hz, 6 H) 2.12 (s, 3 H) 3.70 (s, 3 H) 4.41 (quin, J=6.57 Hz, 1 H) 5.95 (s, 1 H) 6.66 (s, 1 H) 7.01-7.39 (m, 1 H) 7.55-7.88 (m, 2 H) 8.02 (s, 1 H) 8.60 (s, 1 H) 9.76 (br. s., 1 H) 12.01 (br. s., 1 H); HPLC Rt=2.50 min, MS (ESI): 449.0, 451.1 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at the room temperature over the weekend
  2. additionwere added
  3. extractionthe reaction mixture was extracted with 2×50 ml of ethyl acetate
  4. washThe organic layer was washed with 2×50 ml
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe resulting yellow oil was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-ba8ab3333608462994237cbc2d6c127d
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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