Butyramide → HCID 60105793, compound

HRID 393350

Reaction equation

HRID 393350 reaction equation
CS(O[CH2:6][CH:7]1[CH2:11][C:10](=[O:12])[N:9]([C@H:13]([C:16]([NH2:18])=[O:17])[CH2:14][CH3:15])[CH2:8]1)(=O)=O.[N-:19]=[N+:20]=[N-:21].[Na+].FCC1CN([C@@H](CC)C(N)=O)C(=O)C1.O=C1CC(CN2C=NN=N2)CN1[C@@H](CC)C(N)=O.O=C1CC(CN2C=NC=N2)CN1[C@@H](CC)C(N)=O.O=C1CC(CN2C=CN=N2)CN1C(CC)C(N)=O.C(SCC1CN([C@@H](CC)C(N)=O)C(=O)C1)(C)C.C(N)(=O)CCC.O=C1CC(CN2CCSCC2)CN1[C@@H](CC)C(N)=O>C(#N)C>[N:19]([CH2:6][CH:7]1[CH2:8][N:9]([C@@H:13]([CH2:14][CH3:15])[C:16]([NH2:18])=[O:17])[C:10](=[O:12])[CH2:11]1)=[N+:20]=[N-:21]

Participants

11

Reactant 9

HCID 10927ButyramideHCID 33557Sodium Azide2×HCID 9813710(2S)-2-[2-oxo-4-(1H-tetrazol-1-ylmethyl)-1-pyrrolidinyl]butanamide2×HCID 22387100HCID 22387100, compoundHCID 57478742HCID 57478742, compoundHCID 57478743HCID 57478743, compoundHCID 57478744HCID 57478744, compoundHCID 66725879HCID 66725879, compoundHCID 66725939HCID 66725939, compound

Product 1

HCID 60105793HCID 60105793, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
10 °C

Procedure

In a 3 l three necked flask fitted with mechanical stirrer and reflux condenser, under inert atmosphere, 89.7 g (322 mmoles, 1 eq) of {1-[(1S)-1-(aminocarbonyl)propyl]-5-oxo-3-pyrrolidinyl}methyl methanesulfonate 37 are dissolved in 300 ml of acetonitrile. 27.3 g (419 mmoles, 1.3 eq) of sodium azide are added in one portion, with 150 ml of acetonitrile. The mixture is brought to reflux in 20 min, and stirred overnight. 3.1 g (48 mmoles, 0.2 eq) of sodium azide are added and reflux continued for a total of 44 hours. After cooling down to 10° C., the mixture is filtered, the precipitate washed with 3×50 ml of acetonitrile and the combined organic fractions concentrated to dryness to give 77.3 g of crude 32. It is crystallised from 150 ml of ethyl acetate at 10° C. to give 60 g of pure 32, 82%. Alternatively, (2S)-2-[4-(fluoromethyl)-2-oxo-1-pyrrolidinyl]butanamide 44, (2S)-2-[2-oxo-4-(1H-tetrazol-1-ylmethyl)-1-pyrrolidinyl]butanamide 39, (2S)-2-[2-oxo-4-(1H-tetrazol-1-ylmethyl)-1-pyrrolidinyl]butanamide 40, (2S)-2-[2-oxo-4-(1H-1,2,4-triazol-1-ylmethyl)-1-pyrrolidinyl]butanamide 55, 2-[2-oxo-4-(1H-1,2,3-triazol-1-ylmethyl)-1-pyrrolidinyl]butanamide 56, (2S)-2-{4-[(isopropylsulfanyl)methyl]-2-oxo-1-pyrrolidinyl}butanamide 24, (2S)-2-[2-oxo-4-pyrrolidinylmethyl)-1-pyrrolidinyl]butanamide 15, (2S)-2-[2-oxo-4-(4-thiomorpholinylmethyl)-1-pyrrolidinyl]butanamide 17, are prepared in similar ways, from activated alcohol derivatives, such as mesylates, tosylates or halides.

Workup

  1. temperaturereflux condenser
  2. temperatureto reflux in 20 min
  3. temperaturereflux
  4. customcontinued for a total of 44 hours
  5. filtrationthe mixture is filtered
  6. washthe precipitate washed with 3×50 ml of acetonitrile
  7. concentrationthe combined organic fractions concentrated to dryness
  8. customto give 77.3 g of crude 32
  9. customIt is crystallised from 150 ml of ethyl acetate at 10° C.
  10. customto give 60 g of pure 32, 82%

Sources & evidence

ORD record
ord-8c08c0d3e1f547caaa265cc43d090b32
Source dataset
uspto-grants-2004_10
Patent number
US06806287B2

Linked notes

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