Ethyl Acetate → HCID 5276326, compound

HRID 2307292Notes

Reaction equation

HRID 2307292 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:19]=[C:18]([CH2:20]Cl)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.Cl.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]1[C@H:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[OH:33].C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>CN(C=O)C>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:19]=[C:18]([CH2:20][N:26]4[CH2:31][CH2:30][O:29][CH2:28][C@@H:27]4[C@@H:32]([OH:33])[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[S:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 10249252HCID 10249252, compoundHCID 69860165HCID 69860165, compound

Product 1

HCID 5276326HCID 5276326, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide (Preparation 1, 134 mg) and (S)-(3R)-morpholin-3-yl(phenyl)methanol hydrochloride (Preparation 9, 111 mg) in DMF (3 mL) is treated with diisopropylethylamine (0.5 mL). The mixture is heated at 90° C. overnight. After cooling to room temperature, the solution is poured into ethyl acetate (75 mL) and washed with dilute pH 4 phosphate buffer (10 mL), dilute pH 7 phosphate buffer (10 mL), and brine (10 mL). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue is purified by flash column chromatography (methanol/CH2Cl2, 1-3%) and ethyl acetate-hexanes crystallization to afford 0.13 g of the title compound Physical characteristics. M.p. 129-134° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.60, 8.67, 7.41-7.25, 5.33, 5.07, 4.54, 4.17, 3.88, 3.81, 3.73, 3.6, 3.5-3.4, 2.94, 2.6, 2.4-2.3; HRMS m/z 538.1561 (M+H)+. Anal. Found: C, 62.33; H, 5.25; N, 7.75.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed
  3. additionwith dilute pH 4 phosphate buffer (10 mL)
  4. additiondilute pH 7 phosphate buffer (10 mL), and brine (10 mL)
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by flash column chromatography (methanol/CH2Cl2, 1-3%) and ethyl acetate-hexanes crystallization

Sources & evidence

ORD record
ord-754b4870eed943dda859d225e578dada
Source dataset
uspto-grants-2004_12
Patent number
US06831081B2

Reaction notes

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