Methanol → Methyl 2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole-5-carboxylate

HRID 2275033Notes

Reaction equation

HRID 2275033 reaction equation
Br[C:2]1[CH:22]=[C:21]([O:23][C:24]([F:27])([F:26])[F:25])[C:5]2[N:6]([CH3:20])[C:7]([C:9]3[N:17]([CH2:18][CH3:19])[C:12]4=[N:13][CH:14]=[CH:15][CH:16]=[C:11]4[CH:10]=3)=[N:8][C:4]=2[CH:3]=1.C[OH:29].CCN(C(C)C)C(C)C.O1C[CH2:43][O:42][CH2:41]C1>CN(C1C=CN=CC=1)C.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[CH2:18]([N:17]1[C:12]2=[N:13][CH:14]=[CH:15][CH:16]=[C:11]2[CH:10]=[C:9]1[C:7]1[N:6]([CH3:20])[C:5]2[C:21]([O:23][C:24]([F:25])([F:26])[F:27])=[CH:22][C:2]([C:43]([O:42][CH3:41])=[O:29])=[CH:3][C:4]=2[N:8]=1)[CH3:19]

Participants

8

Reactant 4

HCID 887MethanolHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 1181589255-Bromo-2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole

Product 1

HCID 90032907Methyl 2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole-5-carboxylate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Conditions

Temperature
190 °C

Procedure

5-Bromo-2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole (314 mg, 0.715 mmol), molybdenum hexacarbonyl (94 mg, 0.357 mmol), methanol (0.434 mL, 10.72 mmol), DIPEA (0.250 mL, 1.430 mmol), DMAP (175 mg, 1.430 mmol) and trans-bis(acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II) (34 mg, 0.036 mmol) were dissolved in 1,4-dioxane (12 mL) in a microwave vial. The reaction vessel was sealed and heated in Biotage Initiator microwave to 190° C. for 2 h. After allowing the reaction mixture to cool, LCMS showed ˜37% conversion to the desired product, as well as ˜12% conversion to the hydrolysed product. The reaction mixture was concentrated in vacuo to give the crude product, methyl 2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-7-(trifluoromethoxy)-1H-benzo[d]imidazole-5-carboxylate (512 mg, 1.224 mmol, 171% yield) as a brown gum which was used without further purification.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureto cool

Sources & evidence

ORD record
ord-6cb9d08ed4214cdebbd9a3b9a01547e3
Source dataset
uspto-grants-2015_09
Patent number
US09127003B2

Reaction notes

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