1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 59452209, compound

HRID 2381155Notes

Reaction equation

HRID 2381155 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Br:22][C:23]1[CH:28]=[N:27][CH:26]=[C:25]2[N:29]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([I:42])=[CH:38][C:37]=3[F:43])[C:30]([C:32]([O-])=[O:33])=[CH:31][C:24]=12.[Na+].[CH3:45][C:46]1([CH3:54])[O:50][C@@H:49]([CH2:51][O:52][NH2:53])[CH2:48][O:47]1.CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[CH3:45][C:46]1([CH3:54])[O:50][C@@H:49]([CH2:51][O:52][NH:53][C:32]([C:30]2[N:29]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([I:42])=[CH:38][C:37]=3[F:43])[C:25]3=[CH:26][N:27]=[CH:28][C:23]([Br:22])=[C:24]3[CH:31]=2)=[O:33])[CH2:48][O:47]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298047(R)-O-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)hydroxylamineHCID 68486666HCID 68486666, compound

Product 1

HCID 59452209HCID 59452209, compoundYield 68.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

EDCI (99 mg, 0.52 mmol) and HOBt (78 mg, 0.58 mmol) were added to a suspension of sodium 4-bromo-1-(2-fluoro-4-iodo-benzyl)-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (0.23 g, 0.41 mmol) in THF (4 ml). The suspension was warmed gently for 1 minute before the addition of a solution of O—((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-hydroxylamine (85 mg, 0.58 mmol) in THF (1 ml), followed by DIPEA (73 μl, 0.42 mmol). The reaction mixture was stirred at room temperature for 70 hours, poured into ethyl acetate (40 ml) then washed sequentially with 0.1M HCl (10 ml), saturated NaHCO3 solution (10 ml) and brine (10 ml). The organic layer was isolated then dried over magnesium sulphate and concentrated in vacuo to provide a solid residue. Purification of the residue by flash chromatography (Si-SPE, dichloromethane:ethyl acetate 100:0 to 70:30 to 40:60 to 0:100) afforded the title compound as a waxy white solid (0.17 g, 68%). LCMS (method B): RT=3.51 min, M+H+=604, 606.

Workup

  1. washthen washed sequentially with 0.1M HCl (10 ml), saturated NaHCO3 solution (10 ml) and brine (10 ml)
  2. customThe organic layer was isolated
  3. dry with materialthen dried over magnesium sulphate
  4. concentrationconcentrated in vacuo
  5. customto provide a solid residue
  6. customPurification of the residue by flash chromatography (Si-SPE, dichloromethane:ethyl acetate 100:0 to 70:30 to 40:60 to 0:100)

Sources & evidence

ORD record
ord-d570935987714a948f6593527d744331
Source dataset
uspto-grants-2012_09
Patent number
US08258152B2

Reaction notes

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