Triphenylphosphine → Methyl 4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1h-imidazo[4,5-c]quinolin-1-yl]butane-1-sulfonamide

HRID 9425Notes

Reaction equation

HRID 9425 reaction equation
[CH3:1][CH:2]([S:25]([NH2:28])(=[O:27])=[O:26])[CH2:3][CH2:4][CH2:5][N:6]1[C:18]2[C:17]3[CH:16]=[CH:15][C:14](Br)=[CH:13][C:12]=3[N:11]=[C:10]([NH2:20])[C:9]=2[N:8]=[C:7]1[CH2:21][O:22][CH2:23][CH3:24].B1([C:35]2[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=2)OCCCO1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][CH:2]([S:25]([NH2:28])(=[O:27])=[O:26])[CH2:3][CH2:4][CH2:5][N:6]1[C:18]2[C:17]3[CH:16]=[CH:15][C:14]([C:35]4[CH:36]=[N:37][CH:38]=[CH:39][CH:40]=4)=[CH:13][C:12]=3[N:11]=[C:10]([NH2:20])[C:9]=2[N:8]=[C:7]1[CH2:21][O:22][CH2:23][CH3:24]

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridine2×HCID 68819757Methyl 4-(4-amino-7-bromo-2-ethoxymethyl-1h-imidazo[4,5-c]quinolin-1-yl)butane-1-sulfonamide

Product 1

HCID 68818760Methyl 4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1h-imidazo[4,5-c]quinolin-1-yl]butane-1-sulfonamideYield 97.9%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Methyl 4-(4-amino-7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)butane-1-sulfonamide (0.78 g, 1.7 mmol) and pyridine-3-boronic acid 1,3-propanediol cyclic ester (0.33 g, 2.0 mmol) were coupled according to the method described in Part J of Example 1. The reaction was heated at reflux for 15 hours, at which time additional pyridine-3-boronic acid 1,3-propanediol cyclic ester, palladium acetate, and triphenylphosphine were added, and the reaction was heated for an additional three hours. The work-up procedure used in Part F of Examples 125–135 was followed. The crude product was purified twice by column chromatography on silica gel (eluting with chloroform:CMA in a gradient from 95:5 to 70:30) and then triturated with methanol, isolated by filtration, and dried for eight hours under high vacuum at 100° C. to provide 0.78 g of methyl 4-[4-amino-2-ethoxymethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]butane-1-sulfonamide as off-white needles, mp 216–218° C.

Workup

  1. temperatureThe reaction was heated
  2. additionwere added
  3. temperaturethe reaction was heated for an additional three hours
  4. customThe crude product was purified twice by column chromatography on silica gel (
  5. washeluting with chloroform
  6. customCMA in a gradient from 95:5 to 70:30) and then triturated with methanol
  7. customisolated by filtration
  8. customdried for eight hours under high vacuum at 100° C.

Sources & evidence

ORD record
ord-db20c0a683854d36b57eabfee6614a32
Source dataset
uspto-grants-2006_08
Patent number
US07091214B2

Reaction notes

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