Triethylamine → 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-[(methyloxy)methyl]-1-[1-(2-pyridinyl)ethyl]-1H-imidazo[4,5-c]quinoline

HRID 1043020Notes

Reaction equation

HRID 1043020 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11]([NH:18][CH:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH3:20])=[C:12]([NH2:17])[CH:13]=[N:14]3)=[CH:9][C:8]=2[O:27][CH3:28])=[C:5]([CH3:29])[O:4][N:3]=1.CC1C([C:36]2C=C3C(C(NCC4SC(C)=NC=4C)=C(C(N)=O)C=N3)=C[C:37]=2[O:58][CH3:59])=C(C)ON=1.COCC(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:27][CH3:28])=[CH:9][C:10]3[C:11]4[N:18]([CH:19]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=5)[CH3:20])[C:36]([CH2:37][O:58][CH3:59])=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:29])[O:4][N:3]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 12251Methoxyacetic AcidHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574655937-(3,5-Dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinecarboxamideHCID 706626607-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[1-(2-pyridinyl)ethyl]-3,4-quinolinediamine

Product 1

HCID 529345047-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-[(methyloxy)methyl]-1-[1-(2-pyridinyl)ethyl]-1H-imidazo[4,5-c]quinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[1-(2-pyridinyl)ethyl]-3,4-quinolinediamine (for a preparation see Intermediate 65, 250 mg) in DCM (20 ml) was added (methyloxy)acetic acid (116 mg) followed by HATU (1.2 equiv) and triethylamine (1.5 equiv). The reaction mixture was stirred at room temperature for 1 h, and was then hydrolysed using a saturated solution of sodium hydrogen carbonate. The mixture was extracted with DCM and the organic dried over Na2SO4, filtered and concentrated to dryness. The resulting product was dissolved in ethanol (60 ml) and a solution of sodium hydroxide (1N, 15 ml) was added. The reaction mixture was heated to 90° C. for 16 h and was then allowed to cool to room temperature. DCM (150 ml) and water (100 ml) were added. The phases were separated and the organic phase was dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel chromatography eluting with DCM/methanol (95:5). The resulting residue was taken-up in acetonitrile, washed with diethyl ether and dried in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-2-[(methyloxy)methyl]-1-[1-(2-pyridinyl)ethyl]-1H-imidazo[4,5-c]quinoline (90 mg) as a beige powder.

Workup

  1. extractionThe mixture was extracted with DCM
  2. dry with materialthe organic dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. dissolutionThe resulting product was dissolved in ethanol (60 ml)
  6. additiona solution of sodium hydroxide (1N, 15 ml) was added
  7. temperatureThe reaction mixture was heated to 90° C. for 16 h
  8. temperatureto cool to room temperature
  9. additionDCM (150 ml) and water (100 ml) were added
  10. customThe phases were separated
  11. dry with materialthe organic phase was dried over Na2SO4
  12. filtrationfiltered
  13. customevaporated to dryness
  14. customThe residue was purified by silica gel chromatography
  15. washeluting with DCM/methanol (95:5)
  16. washwashed with diethyl ether
  17. customdried in vacuo

Sources & evidence

ORD record
ord-9d15f6fdc9c442979dac0b9d2393975f
Source dataset
uspto-grants-2013_10
Patent number
US08557984B2

Reaction notes

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