Acetonitrile → {3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(3-trifluoromethyl-pyridin-2-yl)-methanol

HRID 886554Notes

Reaction equation

HRID 886554 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH:10]=1.Br[C:38]1[CH:39]=[C:40]([CH:44]([C:46]2[C:51]([C:52]([F:55])([F:54])[F:53])=[CH:50][CH:49]=[CH:48][N:47]=2)[OH:45])[CH:41]=[CH:42][CH:43]=1.C(#N)C.C(=O)(O)[O-].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].ClCCl.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:42]3[CH:41]=[C:40]([CH:44]([C:46]4[C:51]([C:52]([F:55])([F:54])[F:53])=[CH:50][CH:49]=[CH:48][N:47]=4)[OH:45])[CH:39]=[CH:38][CH:43]=3)[CH:16]=2)[N:11]([S:27]([C:30]2[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=2)(=[O:29])=[O:28])[CH:10]=1

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 516892Sodium Bicarbonate2×HCID 160390673-(2-Methoxyphenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 59824996(3-Bromo-phenyl)-(3-trifluoromethyl-pyridin-2-yl)-methanol

Product 1

HCID 59824986{3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(3-trifluoromethyl-pyridin-2-yl)-methanolYield 63%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

504 mg (1.00 mmol) of 3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine, 50 mg (61 μmol) of dichloro[1,1′-bis(diphenylphoshino)ferrocene]-palladium(II) dichloromethane adduct and 337 mg (1.01 mmol) of (3-bromo-phenyl)-(3-trifluoromethyl-pyridin-2-yl)-methanol were place in a microwave vial. 8 mL of acetonitrile, 3 mL of toluene and 8 mL of a saturated aqueous solution of sodium bicarbonate were added. The vial was sealed and irradiated in a Personal Chemistry® Optimizer to 125° C. for 20 min. The resulting mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulfate and evaporated. The resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes to afford 397 mg (0.63 mmol, 63%) of {3-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(3-trifluoromethyl-pyridin-2-yl)-methanol as an ivory solid. 1H NMR (500 MHz, DMSO-d6) δ 8.45 (d, 1H), 8.65 (d, 1H), 8.19 (dd, 1H), 8.09 (d, 2H), 8.07 (d, 1H), 8.06 (s, 1H), 7.75 (s, br., 1H), 7.61-7.58 (m, 1H), 7.53 (dd, 1H), 7.45 (d, 2H), 7.43-7.40 (m, 2H), 7.35 (d(m), 1H), 7.21 (d, 1H), 7.09 (dd(d), 1H), 6.24 (d, 1H), 6.09 (d, 1H), 3.83 (s, 3H), 2.36 (s, 3H); MS: m/z 630.1 (M+H+).

Workup

  1. customThe vial was sealed
  2. customirradiated in a Personal Chemistry® Optimizer to 125° C. for 20 min
  3. extractionThe aqueous layer was extracted twice with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe resulting residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c5fe46e0c60b45ecbc07b38f06288a02
Source dataset
uspto-grants-2012_08
Patent number
US08242280B2

Reaction notes

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