Acetyl chloride → HCID 59556726, compound

HRID 1172959Notes

Reaction equation

HRID 1172959 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]2[C:17]([CH3:23])=[C:18]([C:20](O)=O)[N:19]=[C:13]2[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[Cl:30][C:31]1[CH:32]=[C:33]([CH:38]=[CH:39][C:40]=1[O:41][CH:42]([CH3:44])[CH3:43])/[C:34](=[N:36]\[OH:37])/[NH2:35].C(Cl)(=O)C>C(Cl)Cl.N1C=CC=CC=1.CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]2[C:17]([CH3:23])=[C:18]([C:20]3[O:37][N:36]=[C:34]([C:33]4[CH:38]=[CH:39][C:40]([O:41][CH:42]([CH3:44])[CH3:43])=[C:31]([Cl:30])[CH:32]=4)[N:35]=3)[N:19]=[C:13]2[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6367Acetyl chlorideHCID 65578Oxalyl chlorideHCID 59556734HCID 59556734, compoundHCID 152766118HCID 152766118, compound

Product 1

HCID 59556726HCID 59556726, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 7-(benzyloxycarbony)-3-methy-5,6,7,8-tetrahydroimidazo[1,2-a] pyrazine-2-carboxylic acid (370 mg, 1.173 mmol) in DCM (10m1) was added oxalyl chloride (2.054 ml, 23.47 mmol) and DMF (5 uL). The reaction was stirred for one hour and concentrated. A solution of (E)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (268 mg, 1.173 mmol) in pyridine (10.00 ml) was added and the reaction was stirred at room temperature for 30 minutes. The reaction was treated with acetyl chloride (0.092 ml, 1.291 mmol) and then was heated at 115° C. under nitrogen for 4 hours. The reaction was cooled, concentrated and partitioned between saturated Na2CO3 and methylene chloride. The organic layer was washed with water, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified on silica gel using 80:20/methylene chloride:ethyl acetate as the eluant to yield 2-[3-(3-Chloro-4-isopropoxy -phenyl)-[1,2,4] oxadiazol-5-yl] -3-methyl-5,6-dihydro-8H-imidazo[1,2-a] pyrazine-7-carboxylic acid benzyl ester (173 mg, 29%) as an off-white solid. LCMS (Table 1, Method a) Rl=4.34 min, m/z 508.24 (M+H)+; 1H NMR (400 MHz, DMSO-d6)δ 7.98 (d, 1 H), 7.93 (d,d, 1 H), 7.35 (m, 6H), 5.12 (s, 2H), 4.78 (m, 1 H), 4.66 (s,broad, 2H), 3.99 (m, 2H), 3.88 (s, broad, 2H), 2.57 (s, 3H), 1.31 (d, 6H).

Workup

  1. concentrationconcentrated
  2. stirringthe reaction was stirred at room temperature for 30 minutes
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. custompartitioned between saturated Na2CO3 and methylene chloride
  6. washThe organic layer was washed with water
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on silica gel using 80:20/methylene chloride

Sources & evidence

ORD record
ord-efcb65eac8f34dd68c283139a15895c6
Source dataset
uspto-grants-2010_11
Patent number
US07834039B2

Reaction notes

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