4-Methylmorpholine → phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl) heptanoyl]-1-pyrazolidinecarboxylate

HRID 1396942Notes

Reaction equation

HRID 1396942 reaction equation
[CH:1]([N:3]([CH2:12][C@@H:13]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[C:14]([N:16]1[C@H:20]([C:21]([OH:23])=O)[CH2:19][CH2:18][N:17]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])=[O:15])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:2].CN1CCOCC1.F[B-](F)(F)F.COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[F:68][C:69]1[CH:70]=[CH:71][C:72]([NH2:75])=[N:73][CH:74]=1>C(#N)C>[F:68][C:69]1[CH:70]=[CH:71][C:72]([NH:75][C:21]([C@@H:20]2[CH2:19][CH2:18][N:17]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[N:16]2[C:14](=[O:15])[C@@H:13]([CH2:12][N:3]([CH:1]=[O:2])[O:4][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:23])=[N:73][CH:74]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 27377012-Amino-5-fluoropyridineHCID 116312684-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborateHCID 86706375(3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Product 1

HCID 86706376phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl) heptanoyl]-1-pyrazolidinecarboxylateYield 69.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (1.015 g, 1.931 mmol) in acetonitrile (30 mL) at 0° C. was added 4-methylmorpholine (0.467 mL, 4.25 mmol), followed by 4-[4,6-bis(methyloxy)-1,3,5-triazin-2-yl]-4-methylmorpholin-4-ium tetrafluoroborate (DMTMM) (0.559 g, 2.317 mmol). The solution was stirred for 15 min, then 5-fluoro-2-pyridinamine (0.260 g, 2.317 mmol) was added. The reaction mixture was warmed up to room temperature and stirred overnight. The solvent was evaporated, and the residue was dissolved in DCM. The solution was washed with 5% aq. NaHSO4 followed by water, and the organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford a crude oil which was purified by RP-HPLC to yield phenylmethyl (3S)-3-{[(5-fluoro-2-pyridinyl)amino]carbonyl}-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-pyrazolidinecarboxylate as a colorless gum (830 mg, 69%). LCMS: (M+H)+: 620.2.

Workup

  1. stirringstirred overnight
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in DCM
  4. washThe solution was washed with 5% aq. NaHSO4
  5. dry with materialthe organic phase was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a crude oil which
  9. customwas purified by RP-HPLC

Sources & evidence

ORD record
ord-612b4afefc244ba39b0c7ee8bdbe11e1
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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