1,2-Dimethoxyethane → HCID 71284647, compound

HRID 1481810Notes

Reaction equation

HRID 1481810 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])=[C:13]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:12]=[C:11]([C:33]2[CH:34]=[C:35]3[C:39](=[CH:40][CH:41]=2)[N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:37](B(O)O)=[CH:36]3)[C:10]=1[CH2:52][CH3:53])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:54]([C:56]1[CH:61]=[CH:60][C:59](I)=[CH:58][CH:57]=1)#[N:55].C([O-])([O-])=O.[Na+].[Na+].COCCOC>O>[CH2:1]([O:8][C:9]1[C:14]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])=[C:13]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:12]=[C:11]([C:33]2[CH:34]=[C:35]3[C:39](=[CH:40][CH:41]=2)[N:38]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:37]([C:59]2[CH:60]=[CH:61][C:56]([C:54]#[N:55])=[CH:57][CH:58]=2)=[CH:36]3)[C:10]=1[CH2:52][CH3:53])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 764674-IodobenzonitrileHCID 71285344HCID 71285344, compound

Product 1

HCID 71284647HCID 71284647, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of the boronic acid obtained in Step 1 (75 mg, 0.10 mmol), 4-cyanoiodobenzene (24 mg, 0.10 mmol) Pd(PPh3)4 (12 mg, 0.01 mmol), Na2CO3 (33 mg, 0.30 mmol), DME (0.9 mL) and H2O (0.1 mL) was stirred under argon at 85° C. for 2 hr. The mixture was then concentrated to dryness and chromatographed (silica gel, ethyl acetate in hexanes 0-15% gradient) to provide tert-butyl 5-(4,6-bis(benzyloxy)-5-((benzyloxy)carbonyl)-3-ethylpyridin-2-yl)-2-(4-cyanophenyl)-1H-indole-1-carboxylate (42 mg, yield: 55%). LC-MS 770.6 [M+H]+, RT 1.16 min. (1 min. Method). This was dissolved in diphenyl ether (1 mL) and heated to 210° C. for 0.5 hr. After cooling the mixture was chromatographed (silica gel, ethyl acetate in hexanes 0-50% gradient) to furnish 6-(2-(4-cyanophenyl)-1H-indol-5-yl)-5-ethyl-4-hydroxy-2-oxo-1,2-dihydropyridine-3-carboxylic acid (29 mg, yield: 80%).

Workup

  1. concentrationThe mixture was then concentrated to dryness
  2. customchromatographed (silica gel, ethyl acetate in hexanes 0-15% gradient)

Sources & evidence

ORD record
ord-906101eb2e1e4916b4a1de40d625d14d
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

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