Triethylamine → [1-(3-Benzyl-5-methyl-6-hydroxy-4-oxo-3,4-dihydro-pyrimidin-2-yl)-2-methyl-propyl]-carbamic acid-t-butyl ester

HRID 1455150Notes

Reaction equation

HRID 1455150 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C@@H:8]([C:12](=[NH:21])[NH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:9]([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C([O:32][C:33](=O)[CH:34]([C:36](Cl)=[O:37])[CH3:35])C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:22])[NH:7][CH:8]([C:12]1[N:13]([CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:33](=[O:32])[C:34]([CH3:35])=[C:36]([OH:37])[N:21]=1)[CH:9]([CH3:11])[CH3:10])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10888271Ethyl 2-chloroformylpropionateHCID 178448380HCID 178448380, compound

Product 1

HCID 135848744[1-(3-Benzyl-5-methyl-6-hydroxy-4-oxo-3,4-dihydro-pyrimidin-2-yl)-2-methyl-propyl]-carbamic acid-t-butyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [(R)-1-(N-Benzyl-carbamimidoyl)-2-methyl-propyl]-carbamic acid t-butyl ester (16.37 g, 53.6 mMol) in CH2Cl2 (150 mL) with cooling at 0° C. was added Et3N (9 mL, 64.3 mMol) followed by 2-chlorocarbonyl-propionic acid ethyl ester (10 g, 60.8 mMol) dropwise over 15 minutes. The reaction was allowed to warm to RT and stirred for 4 h, poured into a separatory funnel, washed with water, brine, dried (Na2SO4), and evaporated to dryness under vacuum. The unpurified acylamidine (˜90% pure by LCMS, MS (ES) m/e (M+H)+434.4) was taken up in DMF (150 mL) and heated to 100° C. with stirring for 18 h. The reaction was concentrated under vacuum and purified by flash chromatography (90:10:1, CH2Cl2:EtOAc:HOAc) then (30:70:1, EtOAc:hexane:HOAc) to give the title compound (8.42 g, 41%) as an off-white solid: MS (ES) m/e 388.2 (M+H)+.

Workup

  1. additionpoured into a separatory funnel
  2. washwashed with water, brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated to dryness under vacuum
  5. temperatureheated to 100° C.
  6. stirringwith stirring for 18 h
  7. concentrationThe reaction was concentrated under vacuum
  8. custompurified by flash chromatography (90:10:1, CH2Cl2:EtOAc:HOAc)

Sources & evidence

ORD record
ord-318c5bb60d974849bf78f63eba24d8e2
Source dataset
uspto-grants-2009_01
Patent number
US07482343B2

Reaction notes

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