Tetrahydrofuran → HCID 21949957, compound

HRID 2215811Notes

Reaction equation

HRID 2215811 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][C:12]([NH2:14])=[O:13])[CH:4]=[CH:3]1.[OH:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:27]=1[NH:26][CH:25]=[C:24]2[C:28](=O)[C:29](OC)=[O:30].CC(C)([O-])C.[K+].C1COCC1>CN(C=O)C>[OH:15][CH2:16][CH2:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:27]=1[NH:26][CH:25]=[C:24]2[C:28]1[C:29](=[O:30])[NH:14][C:12](=[O:13])[C:11]=1[C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[N:2]([CH3:1])[CH:3]=[CH:4]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 114353972-(1-methyl-1H-indol-7-yl)acetamideHCID 21950070HCID 21950070, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 21949957HCID 21949957, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(1-methyl-1H-indol-7-yl)acetamide (105 mg, 0.55 mmol) and methyl 2-(7-hydroxypropyl-1H-indol-3-yl)oxoacetate (146 mg, 0.56 mmol) in DMF (2.0 mL) at 4° C. under N2, was added a 1.0 M solution of potassium tert-butoxide in THF (1.7 mL, 1.7 mmol) dropwise over 25 min. The reaction was heated to 60° C. and stirred for 12 h. The reaction mixture was then cooled to room temperature and quenched with 1.0 N hydrochloric acid (5.0 mL). The mixture was extracted with EtOAc (2×15 mL), washed with saturated NaHCO3 (30 mL), saturated NaCl (30 mL), dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 3:47:50 MeOH/EtOAc/CH2Cl2) gave the title compound (196 mg, 87%) as a red solid, mp 183–185° C. 1H NMR (300 MHz, DMSO-d6) 11.81 (s, 1H), 11.12 (s, 1H), 7.87 (m, 1H), 7.61 (m, 1H), 7.28 (m, 1H), 6.98 (m, 3H), 6.50 (m, 2H), 6.29 (m, 1H), 3.68 (s, 3H), 3.41 (m, 2H), 2.78 (m, 2H), 1.76 (m, 2H). MS (electrospray, m/z) 398 [C24H21N3O3−H]−

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customquenched with 1.0 N hydrochloric acid (5.0 mL)
  3. extractionThe mixture was extracted with EtOAc (2×15 mL)
  4. washwashed with saturated NaHCO3 (30 mL), saturated NaCl (30 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ccddc4fda43e4a969a9ced7debd13472
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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