Ethyl Acetate → (R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate

HRID 1521526Notes

Reaction equation

HRID 1521526 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][NH:16][C@H:17]([CH:18]([CH3:20])[CH3:19])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2].Cl[C:27]1[N:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[C:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:29][N:28]=1.CCN(C(C)C)C(C)C.CCOC(C)=O>C(Cl)Cl.CC(O)C>[C:1]([O:4][CH2:5][C:6]1[C:7]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:8][C:9]2[N:13]3[CH2:14][CH2:15][N:16]([C:27]4[N:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[C:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:29][N:28]=4)[C@H:17]([CH:18]([CH3:19])[CH3:20])[C:12]3=[N:11][C:10]=2[CH:21]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 2780355Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylateHCID 89816096(R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate

Product 1

HCID 117935637(R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylateYield 87.8%

Reagents, catalysts & solvents 1

HCID 21966342Isopropanol methylene chlorideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of (R)-(1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-8-yl)methyl acetate (284 mg, 0.8 mmol), ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate (296 mg, 1.2 mmol, 1.5 eq.) and DIEA (310 mg, 2.4 mmol, 3 eq.) in CH2Cl2/i-PrOH (3 mL/3 mL) was stirred at 80° C. for 16 h. TLC showed compound was consumed completely PE:EtOAc=1:1. The solvents were removed under vacuum and the residue was dissolved in EtOAc (10 mL). Water (10 mL) was added to the mixture. The mixture was extracted with EtOAc (10 mL×3). The organic layers were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The residue was purified by column chromatography on silica gel eluting with PE:EtOAc 5:1 to give (R)-ethyl 2-(8-(acetoxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)-4-(trifluoromethyl)pyrimidine-5-carboxylate (0.41 g, 87% yield) as a pale yellow solid.

Workup

  1. customwas consumed completely PE
  2. customThe solvents were removed under vacuum
  3. dissolutionthe residue was dissolved in EtOAc (10 mL)
  4. additionWater (10 mL) was added to the mixture
  5. extractionThe mixture was extracted with EtOAc (10 mL×3)
  6. dry with materialThe organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by column chromatography on silica gel eluting with PE

Sources & evidence

ORD record
ord-ac7b7cf27108491e80ed52912f5cf05d
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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