Ethyl propiolate → HCID 89650589, compound

HRID 2174250Notes

Reaction equation

HRID 2174250 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C:13]2[CH:14]=[N:15][C:16]([NH:27][C:28](=[O:32])[NH:29][CH2:30][CH3:31])=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[O:12])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[C:33]([O:37][CH2:38][CH3:39])(=[O:36])[C:34]#[CH:35]>CN(C=O)C>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([NH:19][C:18]2[CH:17]=[C:16]([NH:27][C:28](=[O:32])[NH:29][CH2:30][CH3:31])[N:15]=[CH:14][C:13]=2[C:11]([NH:10][C:7]2[CH:6]=[CH:5][C:4]([N:1]3[CH:35]=[C:34]([C:33]([O:37][CH2:38][CH3:39])=[O:36])[N:3]=[N:2]3)=[CH:9][CH:8]=2)=[O:12])=[CH:21][CH:22]=1

Participants

4

Reactant 2

HCID 12182Ethyl propiolateHCID 89650766HCID 89650766, compound

Product 1

HCID 89650589HCID 89650589, compoundYield 8.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Compound 132 (50 mg, 0.11 mmol) in DMF (1.8 mL) was added ethyl prop-2-ynoate (21 mg, 0.2218 mmol), followed by ethyl-diiopropylamine (0.023 mL, 0.13 mmol) and cuprous iodide (3.8 mg, 0.020 mmol) at 0° C. The ice bath was removed and the mixture stirred at RT for 2 hours. Water was added and the mixture extracted with EtOAc (4 times). The organic fractions were combined and concentrated in vacuo to give a residue that was purified by medium pressure chromatography (C18 column), eluting with ACN gradient in water, to give target product. The product was triturated with EtOAc to give Compound 133 (5 mg). 1H NMR (400 MHz, DMSO) δ 10.55 (s, 1H), 9.82 (5, 1H), 9.43 (s, 1H), 9.12 (s, 1H), 8.62 (s, 1H), 7.94 (t, J=6.4 Hz, 5H), 7.44 (d, J=8.5 Hz, 2H), 7.31 (d, J=8.5 Hz, 2H), 7.26 (s, 1H), 4.37 (q, J=7.1 Hz, 2H), 3.20-3.11 (m, 2H), 1.35 (t, J=7.1 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H), [M+H]+ m/z=549.03.

Workup

  1. customThe ice bath was removed
  2. additionWater was added
  3. extractionthe mixture extracted with EtOAc (4 times)
  4. concentrationconcentrated in vacuo
  5. customto give a residue that
  6. customwas purified by medium pressure chromatography (C18 column)
  7. washeluting with ACN gradient in water
  8. customto give target product
  9. customThe product was triturated with EtOAc

Sources & evidence

ORD record
ord-97eaee04c08e4117bcfd465a6d33a198
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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