Oxalyl chloride → 4-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

HRID 245661Notes

Reaction equation

HRID 245661 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:13]([OH:15])=O)[N:7]2[CH3:12].C(Cl)(=O)C(Cl)=O.COC1C=CC=C2C=1C=C(C(Cl)=O)N2C.[NH2:37][C:38]1[CH:43]=[CH:42][C:41]([B:44]2[O:52][C:49]([CH3:51])([CH3:50])[C:46]([CH3:48])([CH3:47])[O:45]2)=[CH:40][C:39]=1[O:53][CH3:54]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1.ClCCl.Cl>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:13]([NH:37][C:38]1[CH:43]=[CH:42][C:41]([B:44]3[O:45][C:46]([CH3:47])([CH3:48])[C:49]([CH3:51])([CH3:50])[O:52]3)=[CH:40][C:39]=1[O:53][CH3:54])=[O:15])[N:7]2[CH3:12]

Participants

10

Reactant 4

HCID 65578Oxalyl chlorideHCID 31595784-Methoxy-1-methyl-1H-indole-2-carboxylic acidHCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866746604-methoxy-1-methyl-1H-indole-2-carbonyl chloride

Product 1

HCID 673656514-methoxy-N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideYield 99.9%

Reagents, catalysts & solvents 5

HCID 6344DichloromethaneCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 313Hydrochloric AcidSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 4-methoxy-1-methyl-1H-indole-2-carboxylic acid (24.4 mmol, 5 g) and oxalyl chloride (24.4 mmol, 2.3 mL) in dichloromethane (60 mL) N,N-dimethylformamide (1.22 mmol, 95 μL) was added and the mixture was stirred at room temperature until it formed a clear solution (approximately 4 hours). The mixture was concentrated in vacuo. The residue, 4-methoxy-1-methyl-1H-indole-2-carbonyl chloride, was added to a solution of 4-amino-3-methoxyphenylboronic acid pinacol ester (24.2 mmol, 6.03 g) and 4-dimethylaminopyridine (2.419 mmol, 0.296 g) in pyridine (30 mL) and dichloromethane (30 mL). After stirring at room temperature overnight the reaction mixture was diluted with dichloromethane and 2N hydrochloric acid. The organic layer was separated and the aqueous layer extracted with dichloromethane. The combined organic layers were dried (sodium sulfate) and concentrated in vacuo to yield 10.55 g of the title compound.

Workup

  1. customformed a clear solution (approximately 4 hours)
  2. concentrationThe mixture was concentrated in vacuo
  3. stirringAfter stirring at room temperature overnight the reaction mixture
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried (sodium sulfate)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ea2a8a69d0844001ab4f721623d537d3
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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