3-Iodo-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-1H-indole → 3-Butyl-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-1H-indole

HRID 2234110Notes

Reaction equation

HRID 2234110 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].I[C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[C:16]1[CH:21]=[C:20]([C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)[N:19]=[N:18][C:17]=1[O:28][CH3:29]>C1COCC1.[Cl-].[Zn+2].[Cl-].[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:1]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][C:8]=1[C:16]1[CH:21]=[C:20]([C:22]2[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=2)[N:19]=[N:18][C:17]=1[O:28][CH3:29])[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 2

HCID 231029143-Iodo-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-1H-indoleHCID 178418339Butyllithium

Product 1

HCID 686385773-Butyl-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-1H-indole

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

0.39 ml of n-butyllithium solution (1.6M in hexane) is added at −75° C. to a 0.5 M solution of zinc chloride in THF and the resulting mixture stirred for 30 min at room temperature. This solution is added via a syringe to a solution of 107 mg 3-iodo-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-1H-indole (9b) and 10 mg 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride (1:1 complex with CH2Cl2) in THF and stirred for 4 h at 70° C. The reaction mixture is quenched by adding saturated NH4Cl-solution and extracted with ethylacete. The combined organic layers are dried over MgSO4, the solvens removed in vacuo. Reversed phase chromatography (RP18, water (0.05% HCOOH)/acetonitrile (0.05% HCOOH)) 30 mg product.

Workup

  1. stirringstirred for 4 h at 70° C
  2. customThe reaction mixture is quenched
  3. additionby adding saturated NH4Cl-solution
  4. extractionextracted with ethylacete
  5. dry with materialThe combined organic layers are dried over MgSO4
  6. customthe solvens removed in vacuo

Sources & evidence

ORD record
ord-ce0752f0270045b5b9b1a220592a7eee
Source dataset
uspto-grants-2010_05
Patent number
US07709466B2

Reaction notes

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