2-Methylpyrrolidine → HCID 66723387, compound

HRID 562133Notes

Reaction equation

HRID 562133 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][NH:3]1.[CH:7]([C:9]1[S:13][C:12]([B:14]([OH:16])[OH:15])=[CH:11][CH:10]=1)=O.[BH3-]C#N.[Na+]>CO.C([O-])(O)=O.[Na+]>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][C:9]1[S:13][C:12]([B:14]([OH:16])[OH:15])=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 130032-MethylpyrrolidineHCID 27734305-Formyl-2-thiopheneboronic acidHCID 5003444Sodium cyanoborohydride

Product 1

HCID 66723387HCID 66723387, compoundYield 10.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Batch 3: 2-Methylpyrrolidine (0.033 mL, 0.32 mmol) was added to a solution of (5-formyl-2-thienyl)boronic acid (50 mg, 0.32 mmol) in MeOH (1 mL) in a 2-dram vial. The vial was capped and the reaction was stirred at room temperature for 2 h. NaCNBH3 (40 mg, 0.64 mol) was added, and stirring continued for 19 h. The reaction mixture was loaded directly onto a 2 g SCX cartridge (pre-equilibrated with MeOH), eluting in sequence with MeOH (12 mL) and a 2 M solution of NH3/MeOH (9 mL). The fractions containing the boronic acid crude product were concentrated under a stream of N2 and dried under high vacuum to give 45 mg of crude product. The crude product was taken up in saturated NaHCO3 (2 mL) and extracted with EtOAc (3×2 mL) to give 7.8 mg of crude {5-[(2-methyl-1-pyrrolidinyl)methyl]-2-thienyl}boronic acid. The crude boronic acid from the above three reactions were pooled and carried on for the preparation of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{5-[(2-methyl-1-pyrrolidinyl)methyl]-2-thienyl}-1H-indole-7-carboxamide (final weight after pooling the three batches of {5-[(2-methyl-1-pyrrolidinyl)methyl]-2-thienyl}boronic acid was 19 mg).

Workup

  1. customThe vial was capped
  2. stirringstirring
  3. waitcontinued for 19 h
  4. washeluting in sequence with MeOH (12 mL)
  5. additionThe fractions containing the boronic acid crude product
  6. concentrationwere concentrated under a stream of N2
  7. customdried under high vacuum
  8. customto give 45 mg of crude product
  9. extractionextracted with EtOAc (3×2 mL)

Sources & evidence

ORD record
ord-0516fd45c2f7474a98155774a0cbee49
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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