Acetonitrile--water (1/1) → HCID 178511589, compound

HRID 1963848Notes

Reaction equation

HRID 1963848 reaction equation
[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=3)[N:10]=2)=[CH:4][C:5](F)=[N:6][CH:7]=1.[C@H:24]1([NH2:31])[CH2:29][CH2:28][C@H:27]([NH2:30])[CH2:26][CH2:25]1.C(#N)C.O>CS(C)=O>[NH2:30][C@H:27]1[CH2:28][CH2:29][C@H:24]([NH:31][C:5]2[CH:4]=[C:3]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)[N:10]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 18373917Acetonitrile--water (1/1)HCID 58127193HCID 58127193, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178511589HCID 178511589, compoundYield 81.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture of 5′-chloro-2′-fluoro-N-(3-fluorobenzyl)-2,4′-bipyridin-6-amine (725 mg, 2.185 mmol) was added DMSO (7 ml), trans-cyclohexane-1,4-diamine (1996 mg, 17.48 mmol) and TEA (0.609 ml, 4.37 mmol) was stirred at about 100° C. for 20 hours. The reaction was monitored by LC/MS. The crude reaction mixture mixture was cooled to room temperature, diluted with 3 ml DMSO, filtered, and purified by prep HPLC. (there is a general HPLC conditions in the general experimental session). The fractions were concentrated, mixed with 500 ml ethyl acetate, and basified with saturated sodium bicarbonate 120 ml. The ethyl acetate layer was separated, and the basic water layer was extracted with 300 ml ethyl acetate. The ethyl acetate layers were combined and washed with water (3×), saturated salt solution (1×), dried with sodium sulfate, filtered and concentrated to yield a solid. The solid was dissolved in (1:1 ACN/water) filtered and lyapholized to yield 755 mg of the title compound as free-base. LCMS (m/z): 426.3 (MH+), retention time=0.59 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.10-1.43 (m, 4 H) 1.90 (d, J=12.01 Hz, 2 H) 2.01 (d, J=12.01 Hz, 2 H) 2.70-2.84 (m, 1 H) 3.47-3.60 (m, 1 H) 4.48 (s, 2 H) 6.44 (d, J=8.50 Hz, 1 H) 6.51 (s, 1 H) 6.71 (d, J=7.33 Hz, 1 H) 6.79-6.91 (m, 1 H) 7.00 (d, J=9.96 Hz, 1 H) 7.05-7.13 (m, 1 H) 7.15-7.27 (m, 1 H) 7.40 (t, J=7.77 Hz, 1 H) 7.85 (s, 1 H)

Workup

  1. customThe crude reaction mixture mixture
  2. temperaturewas cooled to room temperature
  3. filtrationfiltered
  4. custompurified by prep HPLC
  5. concentrationThe fractions were concentrated
  6. additionmixed with 500 ml ethyl acetate
  7. customThe ethyl acetate layer was separated
  8. extractionthe basic water layer was extracted with 300 ml ethyl acetate
  9. washwashed with water (3×), saturated salt solution (1×)
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto yield a solid
  14. filtrationfiltered

Sources & evidence

ORD record
ord-cb0b9a11077b4e38af8a81c3a13e53dc
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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