Triethylamine → HCID 22242733, compound

HRID 891708Notes

Reaction equation

HRID 891708 reaction equation
[C:1]([CH2:4][N:5]([CH:18]([CH3:20])[CH3:19])[C:6]([C:8]1[N:9]=[C:10]([N:13]2[CH2:16][CH:15]([OH:17])[CH2:14]2)[S:11][CH:12]=1)=[O:7])(=[O:3])[NH2:2].[CH3:21][S:22](Cl)(=[O:24])=[O:23].C(N(CC)CC)C>C(Cl)Cl>[C:1]([CH2:4][N:5]([CH:18]([CH3:20])[CH3:19])[C:6]([C:8]1[N:9]=[C:10]([N:13]2[CH2:14][CH:15]([O:17][S:22]([CH3:21])(=[O:24])=[O:23])[CH2:16]2)[S:11][CH:12]=1)=[O:7])(=[O:3])[NH2:2].[C:1]([CH2:4][N:5]([CH:18]([CH3:20])[CH3:19])[C:6]([C:8]1[N:9]=[C:10]([N:13]2[CH2:16][CH:15]([O:17][S:22]([CH3:21])(=[O:24])=[O:23])[CH2:14]2)[S:11][CH:12]=1)=[O:7])#[N:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 22242947N-(2-Amino-2-oxoethyl)-2-(3-hydroxy-1-azetidinyl)-N-(1-methylethyl)-4-thiazolecarboxamide

Product 2

HCID 22242719HCID 22242719, compoundYield 17%HCID 22242733HCID 22242733, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-[4-(N-carbamoylmethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]-3-hydroxyazetidine (2.35 g, 7.88 mmol) (obtained as described in Reference Example 49(4)) in methylene chloride (120 ml) were added methanesulfonyl chloride (0.91 ml, 11.8 mmol) and triethylamine (1.66 ml, 11.8 mmol) in an ice bath. The reaction mixture was stirred in the ice bath for 2 hours. After checking the completion of the reaction, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution. The obtained organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using ethyl acetate:methanol (10:1) as the eluant to afford 1-[4-(N-carbamoylmethyl-N-isopropyl-carbamoyl)-1,3-thiazol-2-yl]-3-methanesulfonyloxyazetidine (516 mg, yield 17%) as a pale yellow solid and 1-[4-(cyanomethyl-isopropyl-carbamoyl)-1,3-thiazol-2-yl]-3-methanesulfonyloxyazetidine (634 mg, yield 22%) as a pale yellow solid.

Workup

  1. customthe completion of the reaction
  2. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
  3. washThe obtained organic layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-a5ddc3b5079541a7b2f71826388272ed
Source dataset
uspto-grants-2006_02
Patent number
US07001897B2

Reaction notes

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