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

HRID 1396952Notes

Reaction equation

HRID 1396952 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](O)=[O:22])[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].[N:39]1[CH:44]=[CH:43][CH:42]=[C:41]([NH2:45])[N:40]=1.ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1>C(#N)C.C(OCC)(=O)C>[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]([NH:45][C:41]2[N:40]=[N:39][CH:44]=[CH:43][CH:42]=2)=[O:22])[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:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 230373AminopyridazineHCID 86706375(3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Product 1

HCID 86706386Phenylmethyl (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-3-[(3-pyridazinylamino)carbonyl]-1-pyrazolidinecarboxylateYield 80.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (590 mg, 0.95 mmol), 3-pyridazinamine (100 mg, 1.05 mmol) and 2-chloro-4,6-bis(methyloxy)-1,3,5-triazine (183 mg, 1.05 mmol) in acetonitrile (30 mL) under N2 was added 4-methylmorpholine (212 mg, 2.1 mmol) dropwise. The mixture was stirred at rt overnight. TLC showed that the reaction was complete. The mixture was diluted with ethyl acetate and washed with 5% citric acid, followed by brine. The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography eluting with petroleum ether/ethyl acetate (2:1) to provide the titled compound (460 mg, 79%)

Workup

  1. washwashed with 5% citric acid
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography
  6. washeluting with petroleum ether/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-c425234d62644c69b81baa20df394d50
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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