Cesium carbonate → tert-Butyl 4-(6-(3,4-dimethoxyphenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

HRID 2205892Notes

Reaction equation

HRID 2205892 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:12]3[CH:13]=[N:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:16]=3)[N:10]([CH3:11])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:30][O:31][C:32]1[CH:33]=[C:34]([CH:36]=[CH:37][C:38]=1[O:39][CH3:40])[NH2:35].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[CH3:30][O:31][C:32]1[CH:33]=[C:34]([NH:35][C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[C:9]([C:12]4[CH:13]=[N:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:16]=4)[N:10]([CH3:11])[C:4]=3[CH:3]=2)[CH:36]=[CH:37][C:38]=1[O:39][CH3:40]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 227703,4-DimethoxyanilineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86706281tert-Butyl 4-(6-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 86706305tert-Butyl 4-(6-(3,4-dimethoxyphenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylateYield 11%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd2(dba)3 (9.2 mg, 0.01 mmol) was added to a mixture of tert-butyl 4-(6-bromo-1-methyl-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (28) (38 mg, 0.101 mmol), cesium carbonate (66 mg, 0.201 mmol), 3,4-dimethoxyaniline (18.5 mg, 0.121 mmol) and Xantphos (11.7 mg, 0.020 mmol) in dioxane (1.1 mL). The reaction mixture was heated at 80° C. for 19 hr. The reaction mixture was then filtered and the solution was concentrated under reduced pressure. The residue was purified by prep TLC (DCM/MeOH 95/5) to afford the title compound as a dark red solid (5 mg, 11%). 1H NMR (500 MHz, CDCl3) 1.71 (s, 9H), 3.50 (s, 1H), 3.89 (s, 1H), 3.91 (s, 1H), 6.48 (s, 1H), 6.57 (d, J=0.6 Hz, 1H), 6.64 (m, 1H), 6.89 (m, 2H), 6.92 (m, 1H), 7.91 (d, J=0.6 Hz, 1H), 8.26 (d, J=0.6 Hz, 1H), 8.49 (s, 1H).

Workup

  1. filtrationThe reaction mixture was then filtered
  2. concentrationthe solution was concentrated under reduced pressure
  3. customThe residue was purified by prep TLC (DCM/MeOH 95/5)

Sources & evidence

ORD record
ord-97fdd5b3b27e4db0bbe8c651be327315
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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