Acetic Acid → HCID 57732834, compound

HRID 1806497Notes

Reaction equation

HRID 1806497 reaction equation
[CH2:1]([NH2:4])[CH:2]=[CH2:3].[CH3:5]C(O)=O.[CH2:9]([S:11]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:28]3[C:23](=[C:24]([C:36]([NH2:38])=[O:37])[CH:25]=[C:26]([C:29]4[CH:33]=[C:32]([CH:34]=O)[S:31][CH:30]=4)[CH:27]=3)[NH:22][CH:21]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[CH3:10].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[BH3-]C#N.[Na+].C=O>CS(C)=O.CO>[CH2:9]([S:11]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[C:28]3[C:23](=[C:24]([C:36]([NH2:38])=[O:37])[CH:25]=[C:26]([C:29]4[CH:33]=[C:32]([CH2:34][N:4]([CH3:5])[CH2:1][CH:2]=[CH2:3])[S:31][CH:30]=4)[CH:27]=3)[NH:22][CH:21]=2)[CH2:16][CH2:15]1)(=[O:13])=[O:12])[CH3:10]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 712FormaldehydeHCID 7853AllylamineHCID 5003444Sodium cyanoborohydrideHCID 5049666Sodium triacetoxyborohydrideHCID 577327033-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide

Product 1

HCID 57732834HCID 57732834, compoundYield 23.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

Allylamine (0.034 mL, 0.449 mmol) and HOAc (0.026 mL, 0.449 mmol) were added to a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide (20 mg, 0.0449 mmol) in DMSO (0.5 mL) in a 1-dram vial. NaBH(OAc)3 (95 mg, 0.449 mmol) was then added, the vial was capped and the reaction was stirred at room temperature for 15 h. NaCNBH3 (28 mg, 0.449 mmol) and MeOH were added, and the reaction was stirred for an additional 4 h. An aqueous solution of 37 wt % formaldehyde (0.069 mL, 0.898 mmol) was added, and the reaction was stirred for an additional 1 h. The reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH), eluting in sequence with MeOH (3 mL) and a 2 M solution of NH3/MeOH (9 mL). The NH3/MeOH fraction was concentrated under a stream of nitrogen at 50° C., and the residue was dissolved in DMSO (1 mL) and purified on a Gilson HPLC (Xbridge Prep C18 column: 19×100 mm) eluting at 20 mL per min with a linear gradient running from 10% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 15 min. The fractions containing the title compound were concentrated under a stream of nitrogen at 50° C. to give 5.2 mg of the title compound (23%).

Workup

  1. customthe vial was capped
  2. stirringthe reaction was stirred for an additional 4 h
  3. stirringthe reaction was stirred for an additional 1 h
  4. filtrationThe reaction mixture was filtered through a 2 g SCX cartridge (pre-equilibrated with 3 mL MeOH)
  5. washeluting in sequence with MeOH (3 mL)
  6. concentrationThe NH3/MeOH fraction was concentrated under a stream of nitrogen at 50° C.
  7. dissolutionthe residue was dissolved in DMSO (1 mL)
  8. custompurified on a Gilson HPLC (Xbridge Prep C18 column: 19×100 mm)
  9. washeluting at 20 mL per min with a linear gradient
  10. waitrunning from 10% CH3CN/H2O (0.1% NH4OH) to 70% CH3CN/H2O (0.1% NH4OH) over 15 min
  11. additionThe fractions containing the title compound
  12. concentrationwere concentrated under a stream of nitrogen at 50° C.

Sources & evidence

ORD record
ord-119c09a1373c4b91b694f00ada7b83fd
Source dataset
uspto-grants-2013_01
Patent number
US08354406B2

Reaction notes

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