Dimethylformamide → 5-[4-(azetidin-3-yl)phenyl]-6-chloro-1H-indole-3-carbaldehyde
Reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.CN(C=O)C.[C:24]([O-:27])([O-])=O.[K+].[K+].Br[C:31]1[CH:36]=[CH:35][C:34]([CH:37]2[CH2:40][NH:39][CH2:38]2)=[CH:33][CH:32]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH:39]1[CH2:40][CH:37]([C:34]2[CH:35]=[CH:36][C:31]([C:3]3[CH:4]=[C:5]4[C:9](=[CH:10][C:2]=3[Cl:1])[NH:8][CH:7]=[C:6]4[CH:24]=[O:27])=[CH:32][CH:33]=2)[CH2:38]1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (80 mg, 0.30 mmol) in dioxane (2 mL) was added Vilsmeier salt (150 mg, mmol) and DMF (0.1 mL). The resulting mixture was stirred at room temperature for 20 min. The reaction was quenched with 2N K2CO3 (1.5 mL, 3.0 mmol). 3-(4-Bromophenyl)azetidine (64 mg, 0.30 mmol) and Pd(dppf)Cl2 (20 mg, 0.030 mmol) were next added, and then heated to 90° C. for 30 min. The reaction mixture was extracted with ethyl acetate (3 mL×3). The combined organic layers were concentrated in vacuo to afford the title compound (94 mg, quantitative yield), which was used directly for the next step without further purification.
Workup
- temperatureheated to 90° C. for 30 min
- extractionThe reaction mixture was extracted with ethyl acetate (3 mL×3)
- concentrationThe combined organic layers were concentrated in vacuo
Sources & evidence
- ORD record
- ord-ac39a5a783f64f19a5fc620136bb03d9
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08889730B2
Reaction notes
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