Diisopropylethylamine → (R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate

HRID 1483003Notes

Reaction equation

HRID 1483003 reaction equation
[CH:1]([C@H:4]1[NH:9][CH2:8][CH2:7][N:6]2[C:10]3[CH:16]=[C:15]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][C:11]=3[N:12]=[C:5]12)([CH3:3])[CH3:2].Cl[C:26]1[N:31]=[C:30]([CH:32]2[CH2:34][CH2:33]2)[C:29]([C:35]([O:37][CH3:38])=[O:36])=[CH:28][N:27]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CC(O)C>[CH:32]1([C:30]2[C:29]([C:35]([O:37][CH3:38])=[O:36])=[CH:28][N:27]=[C:26]([N:9]3[CH2:8][CH2:7][N:6]4[C:10]5[CH:16]=[C:15]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]([C:21]([O:23][CH3:24])=[O:22])=[CH:13][C:11]=5[N:12]=[C:5]4[C@H:4]3[CH:1]([CH3:3])[CH3:2])[N:31]=2)[CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 83835308Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylateHCID 89815671(R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate2×

Product 1

HCID 89816093(R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylateYield 43.1%

Reagents, catalysts & solvents 1

HCID 21966342Isopropanol methylene chlorideSolvent

Conditions

Temperature
120 °C

Procedure

The mixture of (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (77 mg, 0.22 mmol), methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate (57 mg, 0.26 mmol, 1.2 eq.) and DIEA (172 mg, 1.3 mmol, 6 eq.) in CH2Cl2/i-PrOH (1 mL/1 mL) was stirred at 120° C. for 16 h. TLC showed (R)-methyl 1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate was consumed completely (PE:EtOAc=1:1). Water (10 mL) was added and 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 preparative TLC to afford (R)-methyl 2-(4-cyclopropyl-5-(methoxycarbonyl)pyrimidin-2-yl)-1-isopropyl-7-(methylsulfonyl)-1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazine-8-carboxylate (50 mg, 43% yield) as a colorless oil.

Workup

  1. customwas consumed completely (PE:EtOAc=1:1)
  2. additionWater (10 mL) was added
  3. extractionthe mixture was extracted with EtOAc (10 mL×3)
  4. dry with materialThe organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-822c2fe60d64425f8bf52cccedc725ee
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

Loading…