1,2-Dichloroethane → HCID 46215628, compound

HRID 1472586Notes

Reaction equation

HRID 1472586 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:20]=2[C:21]([OH:23])=O)=[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]=[CH:26][C:25]([F:28])=[CH:24][C:20]=2[C:21]([NH:37][O:38][CH3:39])=[O:23])=[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 66769562HCID 66769562, compound

Product 1

HCID 46215628HCID 46215628, compoundYield 48.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To the solution of 2-[(5-chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluorobenzoic acid (1128 mg, 2.79 mmol) in N,N-dimethylformamide (DMF) (20 mL) was added HOBT (513 mg, 3.35 mmol) followed by EDC (643 mg, 3.35 mmol) and the reaction mixture stirred for 30 min. To this solution was added o-methoxylamine hydrochloride (280 mg, 3.35 mmol) and after 30 min, at 0° C. DIEA (1.460 mL, 8.38 mmol) was added. The reaction mixture was stirred at room temperature 24 hr. Water (100 mL) was added followed by acetic acid (1 mL) and the solution extracted with 2×50 ml of ethyl acetate. The organic layer was separated, washed with 2×50 ml sat KHCO3, brine, dried over MgSO4 and evaporated. The resulting oil was suspended in dichloromethane and filtered. 2-[(5-Chloro-2-{[3-methyl-1-(1-methylethyl)-1H-pyrazol-5-yl]amino}-4-pyridinyl)amino]-5-fluoro-N-(methyloxy)benzamide (620 mg, 1.361 mmol, 48.7% yield) was isolated as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 1.26 (d, J=6.57 Hz, 6 H) 2.10 (s, 3 H) 3.69 (s, 3 H) 4.38 (quin, J=6.57 Hz, 1 H) 5.92 (s, 1 H) 6.50 (s, 1 H) 7.41-7.52 (m, 2 H) 7.58 (dd, J=8.72, 4.67 Hz, 1 H) 7.96 (s, 1 H) 8.46 (s, 1 H) 9.10 (s, 1 H) 11.95 (s, 1 H); HPLC Rt=2.24 min, MS (ESI): 433.4 [M+H]+.

Workup

  1. waitafter 30 min
  2. customat 0° C
  3. stirringThe reaction mixture was stirred at room temperature 24 hr
  4. extractionthe solution extracted with 2×50 ml of ethyl acetate
  5. customThe organic layer was separated
  6. washwashed with 2×50 ml
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. filtrationfiltered

Sources & evidence

ORD record
ord-ce7d0eb8dc8c4015897d5855dd5bc591
Source dataset
uspto-grants-2015_04
Patent number
US09012479B2

Reaction notes

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