HCID 66715760, compound → HCID 68091970, compound

HRID 2271953Notes

Reaction equation

HRID 2271953 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[CH:16][C:15]([C:21]([CH:23]2[CH2:25][CH2:24]2)=[O:22])=[C:14]3[NH:26][CH:27]2[CH2:32][CH2:31][C:30]([N:34](CC=C)CC=C)([CH3:33])[CH2:29][CH2:28]2)[CH:5]=[C:6]([O:9][CH3:10])[C:7]=1[OH:8]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:34][C:30]1([CH3:33])[CH2:31][CH2:32][CH:27]([NH:26][C:14]2[C:13]3[C:18](=[CH:19][CH:20]=[C:11]([C:4]4[CH:5]=[C:6]([O:9][CH3:10])[C:7]([OH:8])=[C:2]([Cl:1])[CH:3]=4)[CH:12]=3)[N:17]=[CH:16][C:15]=2[C:21]([CH:23]2[CH2:25][CH2:24]2)=[O:22])[CH2:28][CH2:29]1

Participants

4

Reactant 1

HCID 66715760HCID 66715760, compound

Product 1

HCID 68091970HCID 68091970, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of {6-(3-chloro-4-hydroxy-5-methoxyphenyl)-4-[4-(diallylamino)-4-methylcyclohexylamino]quinolin-3-yl}(cyclopropyl)methanone (49 mg, 0.088 mmol) in dioxane (3 mL) was added Pd(PPh3)4 (10 mg, 0.008 mmol) and N,N-dimethylbartituric acid (68 mg, 0.438 mmol). The resultant mixture purged with N2 and heated to 80° C. for 16 h. The solution was allowed to cool to rt, diluted with ethyl acetate, filtered and concentrated. The resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA). The purified product was concentrated, diluted with a saturated NaHCO3 solution, extracted with a mixture of CHCl3/isopropanol (3:1), and dried with Na2SO4 to obtain the desired product as the free base (5 mg, 4%) as a yellow solid: 1H NMR (500 MHz, CD3OD+TFA-d) δ 9.14 (s, 1H), 8.34 (s, 1H), 8.00 (dd, J=8.7, 2.0 Hz, 1H), 7.89 (d, J=8.7 Hz, 1H), 7.26 (d, J=2.2 Hz, 1H), 7.20 (d, J=2.2 Hz, 1H), 4.29-4.21 (m, 1H), 3.97 (s, 3H), 2.89-2.80 (m, 1H), 2.14-2.07 (m, 2H), 1.92-1.71 (m, 4H), 1.70-1.61 (m, 2H), 1.28 (s, 3H), 1.25-1.06 (m, 4H); ESI MS m/z 480 [C27H30ClN3O3+H]+; HPLC>99% (AUC), tR=10.46 min.

Workup

  1. customThe resultant mixture purged with N2
  2. temperatureto cool to rt
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resultant residue was purified by preparative HPLC (C18 silica, 10-90% acetonitrile/water with 0.05% TFA)
  7. concentrationThe purified product was concentrated
  8. additiondiluted with a saturated NaHCO3 solution
  9. extractionextracted with a mixture of CHCl3/isopropanol (3:1)
  10. dry with materialdried with Na2SO4

Sources & evidence

ORD record
ord-4a34cffafd1a472796aa61270048e492
Source dataset
uspto-grants-2015_09
Patent number
US09120749B2

Reaction notes

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