Toluene → HCID 117925887, compound

HRID 1054208Notes

Reaction equation

HRID 1054208 reaction equation
[CH2:1]([N:3]1[C:8](=O)[C:7]2[N:10]=[CH:11][CH:12]=[CH:13][C:6]=2[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:4]1)[CH3:2].COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:29]2)=CC=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH2:1]([N:3]1[C:8](=[S:29])[C:7]2[N:10]=[CH:11][CH:12]=[CH:13][C:6]=2[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 1140TolueneHCID 87949Lawesson's reagentHCID 117926657HCID 117926657, compound

Product 1

HCID 117925887HCID 117925887, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-ethyl-5-(pyridin-2-yl)pyrido[2,3-d]pyridazin-8(7H)-one RL-8 (90 mg, 0.36 mmol), 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (145 mg, 0.36 mmol), and toluene (8 mL) was heated to 115° C. for 3.5 h. After cooling to ambient temperature, the reaction mixture was diluted with 20 mL of ethyl acetate and washed with a 1:1 solution of saturated brine/1 N NaOH. The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure and purified by normal phase flash chromatography eluting with 0-10% methanol in dichloromethane over 22 minutes. Like fractions containing the desired product were pooled, concentrated under reduced pressure, and dried overnight at 60° C. under vacuum to give 7-ethyl-5-(pyridin-2-yl)pyrido[2,3-d]pyridazine-8(7H)-thione RL-9 (52 mg, 0.20 mmol). 1H NMR (400 MHz, DMSO-d6) δ 9.17 (dd, J=4.3, 1.7 Hz, 1H), 8.98 (dd, J=8.3, 1.7 Hz, 1H), 8.77 (ddd, J=4.8, 1.7, 1.0 Hz, 1H), 8.08-7.97 (m, 2H), 7.91 (dd, J=8.3, 4.3 Hz, 1H), 7.59 (ddd, J=7.3, 4.8, 1.5 Hz, 1H), 4.86 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H).

Workup

  1. washwashed with a 1:1 solution of saturated brine/1 N NaOH
  2. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. custompurified by normal phase flash chromatography
  6. washeluting with 0-10% methanol in dichloromethane over 22 minutes
  7. additionLike fractions containing the desired product
  8. concentrationconcentrated under reduced pressure
  9. customdried overnight at 60° C. under vacuum

Sources & evidence

ORD record
ord-f69f2c9b00a1481ab20cec84dbd33ca3
Source dataset
uspto-grants-2016_07
Patent number
US09394299B2

Reaction notes

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