N-methyl-N-(trimethylsilyl)trifluoroacetamide → (S)-[1-[[[[[[3-[[(1,4-Dihydro-5-hydroxy-4-oxo-2-pyridinyl)-carbonyl]amino]tetrahydro-2-oxo-1(2H)-pyrimidinyl]carbonyl]amino]-sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester

HRID 2351093Notes

Reaction equation

HRID 2351093 reaction equation
[O:1]=[C:2]1[C@@H:5]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][NH:3]1.Cl[S:18]([N:21]=[C:22]=[O:23])(=[O:20])=[O:19].C(OCC)(=O)C.O=C1NCCCN1NC(=O)OCC1C=CC=CC=1.[OH:48][C:49]1[C:50](=[O:68])[CH:51]=[C:52]([C:55]([NH:57][N:58]2[CH2:63][CH2:62][CH2:61][N:60]([C:64]([NH2:66])=[O:65])[C:59]2=[O:67])=[O:56])[NH:53][CH:54]=1.CN([Si](C)(C)C)C(=O)C(F)(F)F>C(OCC)(=O)C.O.ClCCl>[OH:48][C:49]1[C:50](=[O:68])[CH:51]=[C:52]([C:55]([NH:57][N:58]2[CH2:63][CH2:62][CH2:61][N:60]([C:64]([NH:66][S:18]([NH:21][C:22]([N:3]3[CH2:4][C@H:5]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:2]3=[O:1])=[O:23])(=[O:20])=[O:19])=[O:65])[C:59]2=[O:67])=[O:56])[NH:53][CH:54]=1

Participants

9

Reactant 5

HCID 32510N-methyl-N-(trimethylsilyl)trifluoroacetamideHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamateHCID 19848000Ethyl acetate chlorosulfonyl isocyanateHCID 198480063-[[(1,4-Dihydro-5-hydroxy-4-oxo-2-pyridinyl)carbonyl]-amino]tetrahydro-2-oxo-1(2H)-pyrimidinecarboxamideHCID 54188774(Tetrahydro-2-oxo-1(2H)-pyrimidinyl)carbamic acid, phenylmethyl ester2×

Product 1

HCID 86743425(S)-[1-[[[[[[3-[[(1,4-Dihydro-5-hydroxy-4-oxo-2-pyridinyl)-carbonyl]amino]tetrahydro-2-oxo-1(2H)-pyrimidinyl]carbonyl]amino]-sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl esterYield 55.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (6.61 g, 30.0 mmol) in 300 ml ethyl acetate chlorosulfonyl isocyanate (4.25 g, 30.0 mmol) was added, and the mixture was stirred for 1 hour at room temperature (solution A). To a solution of 3-[[(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)-carbonyl]-amino]tetrahydro-2-oxo-1(2H)-pyrimidinecarboxamide (8.86 g, 30.0 mmol) in 300 ml ethyl acetate, N-methyl-N-trimethylsilyltrifluoroacetamide (23.91 g, 120 mmol) was added. After 30 minutes a clear solution was obtained; 300 ml dichloromethane was added, followed by the dropwise addition of solution A at 0° C. After stirring overnight at room temperature 300 ml water was added whereupon an oily residue separated. The solvents were decanted off and the residue triturated with ether to give 10.27 g of the desired product (crude). The product was suspended in water and the pH adjusted to 6 with 2N sodium hydroxide. After freeze drying of the resulting solution the product was chromatographed in four portions on XAD under mplc conditions with water and water:acetonitrile 9:1 as eluents. The product-containing fractions were freeze dried to give a total of 5.2 g of the desired product.

Workup

  1. additionwas added
  2. customAfter 30 minutes a clear solution was obtained
  3. additionwas added whereupon an oily residue
  4. customseparated
  5. customThe solvents were decanted off
  6. customthe residue triturated with ether

Sources & evidence

ORD record
ord-8f9da80e0f9f468b9b11d30b391a24f7
Source dataset
uspto-grants-1989_10
Patent number
US04871841

Reaction notes

Loading…