Sodium hydride → HCID 67158717, compound

HRID 549054Notes

Reaction equation

HRID 549054 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]([CH3:15])[CH:8]=[C:7]2[C:16]1[N:24]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:19]2=[N:20][CH:21]=[CH:22][CH:23]=[C:18]2[CH:17]=1.[CH2:35]([O:37][C:38]([C:40]1(Br)[CH2:43][CH2:42][CH2:41]1)=[O:39])[CH3:36]>CN(C)C=O>[CH2:35]([O:37][C:38]([C:40]1([O:3][C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][C:12]=2[O:13][CH3:14])[N:9]([CH3:15])[CH:8]=[C:7]3[C:16]2[N:24]([S:25]([C:28]3[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=3)(=[O:27])=[O:26])[C:19]3=[N:20][CH:21]=[CH:22][CH:23]=[C:18]3[CH:17]=2)[CH2:43][CH2:42][CH2:41]1)=[O:39])[CH3:36]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 97595Ethyl 1-bromocyclobutanecarboxylate2×HCID 22477340HCID 22477340, compound

Product 1

HCID 67158717HCID 67158717, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (43 mg, 60% dispersion in mineral oil) was added to a stirred solution of 2-(5-hydroxy-6-methoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine [400 mg, Reference Example 28(a)] in dry dimethylformamide (20 mL) under a nitrogen atmosphere at ambient temperature. The mixture was allowed to stir for 1 hour then treated with ethyl-1-bromocyclobutanecarboxylate (216 μl) and stirring was continued overnight. Additional portions of sodium hydride (43 mg, 60% dispersion in mineral oil) and ethyl 1-bromocyclobutanecarboxylate (216 μl) were then added, then the mixture was heated at 50° C. for 5 hours. The cooled reaction mixture was evaporated and the residue was partitioned between ethyl acetate and water. The organic phase was washed with water, then with brine, then dried over magnesium sulfate and then evaporated. The yellow residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3, v/v) to give the title compound (266 mg) as a yellow oil. MS: 576 (MH+). HPLC (METHOD A): RT=11.07 minutes.

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. customThe cooled reaction mixture
  4. customwas evaporated
  5. customthe residue was partitioned between ethyl acetate and water
  6. washThe organic phase was washed with water
  7. dry with materialwith brine, then dried over magnesium sulfate
  8. customevaporated
  9. additionThe yellow residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (2:3

Sources & evidence

ORD record
ord-105981a9aed64b25b70e95a443a3ca91
Source dataset
uspto-grants-2011_05
Patent number
US07943616B2

Reaction notes

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