Diisopropylethylamine → 4-[3-(1-Pyridin-2-yl-[1,2,4]triazolo[4,3-a]quinolin-7-ylsulfanyl)-phenyl]-tetrahydro-pyran-4-carboxylic acid methyl ester

HRID 2075695Notes

Reaction equation

HRID 2075695 reaction equation
C(C(CCCC)COC(=O)[CH2:7][CH2:8][S:9][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][CH:19]=1)[N:16]1[C:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)=[N:21][N:22]=[C:15]1[CH:14]=[CH:13]2)C.CC(C)([O-])C.[K+].[CH3:40][O:41][C:42]([C:44]1([C:50]2C=C[CH:53]=[C:52](Br)[CH:51]=2)[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1)=[O:43].CCN(C(C)C)C(C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:40][O:41][C:42]([C:44]1([C:50]2[CH:51]=[CH:52][CH:53]=[C:8]([S:9][C:10]3[CH:11]=[C:12]4[C:17](=[CH:18][CH:19]=3)[N:16]3[C:20]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=5)=[N:21][N:22]=[C:15]3[CH:14]=[CH:13]4)[CH:7]=2)[CH2:45][CH2:46][O:47][CH2:48][CH2:49]1)=[O:43]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23665647Potassium tert-butoxideHCID 67091038Methyl 4-(3-bromophenyl)tetrahydro-2H-pyran-4-carboxylateHCID 670910663-(1-Pyridin-2-yl-[1,2,4]triazolo[4,3-a]quinolin-7-ylsulfanyl)-propionic acid 2-ethyl-hexyl ester

Product 1

HCID 670909504-[3-(1-Pyridin-2-yl-[1,2,4]triazolo[4,3-a]quinolin-7-ylsulfanyl)-phenyl]-tetrahydro-pyran-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

5m (216 mg, 0.47 mmol) was dissolved in 1,4-dioxane (5 mL) and degassed with N2 for 20 minutes. Potassium tert-butoxide (55 mg, 0.49 mmol) was added, and the reaction was stirred at room temperature overnight. The mixture was degassed with N2 for an additional 20 minutes, and then 4-(3-Bromo-phenyl)-tetrahydro-pyran-4-carboxylic acid methyl ester (5o, 141 mg, 0.47 mmol) in 1,4-dioxane (1 mL) was added, followed by iPr2NEt (0.18 mL, 1.03 mmol), Pd2dba3 (11 mg, 0.01 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (15 mg, 0.02 mmol). The reaction was sealed and heated to 110° C. for 1.5 hours. The mixture was cooled to room temperature and concentrated, and the residue was purified by silica gel chromatography (20-100% EtOAc in hexanes, followed by 0-10% MeOH in EtOAc) to give the desired product, 5p.

Workup

  1. customdegassed with N2 for 20 minutes
  2. customThe mixture was degassed with N2 for an additional 20 minutes
  3. customThe reaction was sealed
  4. temperatureheated to 110° C. for 1.5 hours
  5. temperatureThe mixture was cooled to room temperature
  6. concentrationconcentrated
  7. customthe residue was purified by silica gel chromatography (20-100% EtOAc in hexanes, followed by 0-10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-a8f63085cfe1485a9b5ff952f6e3c108
Source dataset
uspto-grants-2011_04
Patent number
US07919621B2

Reaction notes

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