Pinacol → HCID 24887406, compound

HRID 1436994Notes

Reaction equation

HRID 1436994 reaction equation
CO[C:3](=[O:23])[CH2:4][CH:5]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]#[N:22])[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[CH:9]2.OC(C(O)(C)C)(C)C.[BH4-].[Na+]>CO>[NH:11]1[C:12]2[C:8](=[CH:7][C:6]([CH:5]3[CH2:4][C:3](=[O:23])[NH:22][CH2:21][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]3=4)=[CH:14][CH:13]=2)[CH:9]=[CH:10]1

Participants

5

Reactant 3

HCID 6425PinacolHCID 4311764Sodium borohydrideHCID 24887405HCID 24887405, compound

Product 1

HCID 24887406HCID 24887406, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of 3-(2-cyano-phenyl)-3-(1H-indol-5-yl)-propionic acid methyl ester and pinacol (1:2 molar ratio, 2.1 g) in methanol (100 mL) was added sodium borohydride (2.6 g, 14 mmol), portionwise over 45 minutes. Stirring continued for 15 hours at room temperature. The reaction mixture was then filtered through Celite, washed with methanol, and the combined filtrates were concentrated. The crude material so obtained was partitioned between ethyl acetate and 5% aqueous ammonium hydroxide. The organic layer was dried over sodium sulfate, filtered and concentrated to a yellow oil which contained a mixture of 5-(1H-Indol-5-yl)-1,2,4,5-tetrahydro-benzo[c]azepin-3-one and uncyclized 3-(2-aminomethyl-phenyl)-3-(1H-indol-5-yl)-propionic acid methyl ester (not shown in Scheme B). This crude oil was suspended in 1,4-dioxane (100 mL) and heated to reflux for 40 hours, then cooled and concentrated to a brown oil and purified by flash chromatography (methanol/ethyl acetate) to afford pure 5-(1H-Indol-5-yl)-1,2,4,5-tetrahydro-benzo[c]azepin-3-one as a white solid (0.50 g). MS (M+H)=277.

Workup

  1. waitcontinued for 15 hours at room temperature
  2. filtrationThe reaction mixture was then filtered through Celite
  3. washwashed with methanol
  4. concentrationthe combined filtrates were concentrated
  5. customThe crude material so obtained
  6. customwas partitioned between ethyl acetate and 5% aqueous ammonium hydroxide
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a yellow oil which
  10. additiona mixture of 5-(1H-Indol-5-yl)-1,2,4,5-tetrahydro-benzo[c]azepin-3-one and uncyclized 3-(2-aminomethyl-phenyl)-3-(1H-indol-5-yl)-propionic acid methyl ester (not
  11. temperatureheated
  12. temperatureto reflux for 40 hours
  13. temperaturecooled
  14. concentrationconcentrated to a brown oil
  15. custompurified by flash chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-4fcc7b9c5ce447cb9aa86cf2a9cd4dc9
Source dataset
uspto-grants-2009_11
Patent number
US07622462B2

Reaction notes

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