Ethylamine hydrochloride → HCID 71599802, compound

HRID 1507692Notes

Reaction equation

HRID 1507692 reaction equation
C([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22](=[O:26])[N:23]([CH3:25])[CH3:24])[N:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:10]=1[C:35]([O:37]CC)=O)C1C=CC=CC=1.Cl.[CH2:41]([NH2:43])[CH3:42].[CH:44]([Mg]Cl)([CH3:46])[CH3:45]>C1COCC1>[CH2:45]([O:8][C:9]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([C:22]([N:23]([CH3:24])[CH3:25])=[O:26])[N:11]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[C:10]=1[C:35]([NH:43][CH2:41][CH3:42])=[O:37])[C:44]1[CH:46]=[CH:35][CH:10]=[CH:9][CH:13]=1

Participants

5

Reactant 3

HCID 11198Ethylamine hydrochloride2×HCID 89610459HCID 89610459, compoundHCID 178418918HCID 178418918, compound2×

Product 1

HCID 71599802HCID 71599802, compoundYield 191.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of ethyl 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylate (6) (200 mg, 0.38 mmol) and ethylamine hydrochloride (61.7 mg, 0.75 mmol) in THF (2 mL) was added isopropylmagnesium chloride (2 M in THF) (757 μL, 1.51 mmol) and the reaction stirred at RT for 2 h, further portions of ethylamine hydrochloride (120 mg, 1.5 mmol) and isopropylmagnesium chloride (2 M in THF) (1.5 mL, 3.0 mmol) were added and the reaction stirred for 16 h at RT. The reaction mixture was partitioned between sat. NH4Cl solution (aq.) (5 mL) and EtOAc (20 mL) the aqueous was further acidified with 1 M HCl (5 mL). The organic layer was separated and washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo to afford crude product. The residue was purified by silica gel chromatography (25 g, 30-80% EtOAc in isohexane) to afford 3,4-bis(benzyloxy)-N2-ethyl-1-(4-methoxyphenyl)-N5,N5-dimethyl-1H-pyrrole-2,5-dicarboxamide (UL1-055) (192 mg, 95%) as a yellow oil: m/z 528 (M+H)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.44-7.30 (m, 10H), 7.20-7.09 (m, 2H), 7.06-6.97 (m, 1H), 6.89-6.80 (m, 2H), 5.20 (s, 2H), 5.07 (s, 2H), 3.79 (s, 3H), 3.25-3.14 (m, 2H), 2.79 (s, 3H), 2.72 (s, 3H), 0.97 (t, J=7.3 Hz, 3H).

Workup

  1. stirringthe reaction stirred for 16 h at RT
  2. customThe reaction mixture was partitioned between sat. NH4Cl solution (aq.) (5 mL) and EtOAc (20 mL) the
  3. customThe organic layer was separated
  4. washwashed with brine (25 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford crude product
  9. customThe residue was purified by silica gel chromatography (25 g, 30-80% EtOAc in isohexane)

Sources & evidence

ORD record
ord-d8e8572ef7ca453caedc733e5b90a401
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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