Ethyl Acetate → HCID 5276325, compound

HRID 2307291Notes

Reaction equation

HRID 2307291 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 69857956HCID 69857956, compound

Product 1

HCID 5276325HCID 5276325, compoundYield 79.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °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 (R)-(3R)-morpholin-3-yl(phenyl)methanol hydrochloride (Preparation 6, 112 mg) in DMF (3 mL) is treated with diisopropylethylamine (0.5 mL). The mixture is heated at 95° C. overnight. After cooling to room temperature, the solution is poured into ethyl acetate (75 mL) and washed with dilute pH 4 phosphate buffer (25 mL), dilute pH 7 phosphate buffer (2×25 mL), and brine (25 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 0.15 g of the title compound. Physical characteristics. M.p. 171-172° C.; 1H NMR(400 MHz, DMSO-d6) δ 10.63, 8.71, 7.4-7.3, 7.3, 5.42, 5.09, 4.55, 4.50, 4.15, 3.97, 3.5, 3.4, 3.04, 2.9, 2.8, 2.4; HRMS m/z 538.1558 (M+H)+. Anal. Found. C, 62.41; H, 5.17; N, 7.73.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed
  3. additionwith dilute pH 4 phosphate buffer (25 mL)
  4. additiondilute pH 7 phosphate buffer (2×25 mL), and brine (25 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-d590bb71934f4aecabaf4112bad8f6f6
Source dataset
uspto-grants-2004_12
Patent number
US06831081B2

Reaction notes

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