Triethylamine → 1-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

HRID 901464Notes

Reaction equation

HRID 901464 reaction equation
[CH3:1][CH:2]([CH3:28])[CH:3]([NH:15][C:16]([CH:18]1[CH2:22][CH:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][NH:19]1)=[O:17])[CH:4]1[CH:9]([OH:10])[CH:8]([OH:11])[CH:7]([OH:12])[CH:6]([S:13][CH3:14])[O:5]1.C(N(CC)CC)C.Br[CH2:37][C:38]([NH2:40])=[O:39]>C(#N)C>[CH3:1][CH:2]([CH3:28])[CH:3]([NH:15][C:16]([CH:18]1[CH2:22][CH:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][N:19]1[CH2:37][C:38](=[O:39])[NH2:40])=[O:17])[CH:4]1[CH:9]([OH:10])[CH:8]([OH:11])[CH:7]([OH:12])[CH:6]([S:13][CH3:14])[O:5]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 696322-BromoacetamideHCID 780406994-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

Product 1

HCID 112829251-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide (200 mg, 0.48 mmol, 1 equiv), in anhydrous acetonitrile (3 mL), at room temperature, under nitrogen atmosphere, was added triethylamine (0.2 mL, 1.44 mmol, 3 equiv) followed by bromoacetamide (80 mg, 0.58 mmol, 1.2 equiv). The resulting mixture was stirred at room temperature for 18 h, and evaporated to dryness. The residue obtained was first purified over silica gel, with an eluant of 7% methanolic-ammonia/dichloromethane. The desired fractions were collected, evaporated to dryness, and repurified by HPLC (to remove, the side-product from the reaction of the base with bromoacetamide). After lyophilization the desired title compound for example 40 was obtained (2.0 mg) as a white fluffy powder: HPLC: Rt=4.11 min (220.0 nm); 1H NMR (300 MHz, CD3OD) δ (rotamers) 5.46 (d, J=5.5, 1), 4.47 (dd, J=3.02, 2.7, 1.1), 4.31-4.25 (m, 3.3), 4.11 (d, J=3.02, 1.6), 2.31 (s, 3), 1.65-1.52 (m, 9.5), 1.12-1.09 (m, 10.3). MS (ESPOS): 476.5 [M+H]+, (ESNEG): 474.5[M−H]−.

Workup

  1. customevaporated to dryness
  2. customThe residue obtained
  3. customwas first purified over silica gel, with an eluant of 7% methanolic-ammonia/dichloromethane
  4. customThe desired fractions were collected
  5. customevaporated to dryness
  6. customrepurified by HPLC (
  7. customto remove
  8. customthe side-product from the reaction of the base with bromoacetamide)

Sources & evidence

ORD record
ord-cf3ed1320d9a421fa7cd65b4b2cf5e7a
Source dataset
uspto-grants-2008_04
Patent number
US07361743B2

Reaction notes

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