Dimethylformamide → HCID 86585285, compound

HRID 2304758Notes

Reaction equation

HRID 2304758 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2C(OC)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:22][N:23]([CH:25]=[O:26])C.[H-].[Na+].[C:29]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=1)([CH3:32])([CH3:31])[CH3:30]>O.C1COCC1>[C:29]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37][N:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:9]([O:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[C:10]2[N:23]([C:22]2[CH:12]=[N:11][CH:10]=[CH:9][CH:17]=2)[CH:25]=[O:26])=[CH:35][CH:34]=1)([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 878361-(Bromomethyl)-4-(1,1-dimethylethyl)benzeneHCID 18435811HCID 18435811, compound

Product 1

HCID 86585285HCID 86585285, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Into a round bottom flask was placed methyl 3-(phenylmethoxy)indole-2-carboxylate (50 mg) along with DMF (1.0 mL), THF (1.0 mL) and 10 mg of a NaH suspension (60% in oil). To this stirred mixture was added 4-tert-butylbenzyl bromide and allowed to stir at room temperature overnight. At this time, the reaction mixture was diluted with H2O, poured into a teflon fritted cartridge and extracted with CH2Cl2. The filtrate was concentrated and then treated with THF/H2O (5.0 mL, 1:1), MeOH (2.0 mL), NaOH (1 mL of a 1N aq. solution) and allowed to stir at room temperature overnight. At this time, the reaction mixture was acidified to pH 4 with an aqueous 1N HCl solution, diluted with 2 mL H2O, extracted with CH2Cl2 through a teflon fritted cartridge as above and the filtrate was concentrated. The resulting crude carboxylic acid was taken up in THF (2.0 mL) and treated with i-Pr2NEt (0.1 mL), MsCl (10 μL) followed by 3-aminopyridine (50 mg) as described previously for the preparation of example 166. After work-up and purification by flash chromatography 10.6 mg of the title amide was isolated.

Workup

  1. customInto a round bottom flask was placed
  2. extractionextracted with CH2Cl2
  3. concentrationThe filtrate was concentrated
  4. additiontreated with THF/H2O (5.0 mL, 1:1), MeOH (2.0 mL), NaOH (1 mL of a 1N aq. solution) and
  5. stirringto stir at room temperature overnight
  6. additiondiluted with 2 mL H2O
  7. extractionextracted with CH2Cl2 through a teflon fritted cartridge as above and the filtrate
  8. concentrationwas concentrated
  9. additiontreated with i-Pr2NEt (0.1 mL), MsCl (10 μL)
  10. customas described previously for the preparation of example 166
  11. customAfter work-up and purification by flash chromatography 10.6 mg of the title amide
  12. customwas isolated

Sources & evidence

ORD record
ord-364030546963484cb3987abcb8c8016d
Source dataset
uspto-grants-2002_08
Patent number
US06436965B1

Reaction notes

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