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

HRID 1396955Notes

Reaction equation

HRID 1396955 reaction equation
[CH:1]([N:3]([CH2:12][C@@H:13]([CH2:34][CH2:35][CH2:36][CH3:37])[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:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[NH2:44].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][CH3:37])[C:14]([N:16]1[C@H:20]([C:21]([NH:44][C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][N:38]=2)=[O:22])[CH2:19][CH2:18][N:17]1[C:24]([O:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=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]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 104392-AminopyridineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 86706343(3S)-2-[(2R)-2-({Formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid2×

Product 1

HCID 86706388Phenylmethyl (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-3-[(2-pyridinylamino)carbonyl]-1-pyrazolidinecarboxylateYield 70%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3S)-2-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)hexanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (Intermediate 4) (150 mg, 0.3 mmol), 2-pyridinamine (32 mg, 0.33 mmol) and 2-chloro-4,6-bis(methyloxy)-1,3,5-triazine (58 mg, 0.33 mmol) in acetonitrile (4 mL) under N2 was added 4-methylmorpholine (65 mg, 0.66 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 to provide the titled compound (110 mg, 70%).

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

Sources & evidence

ORD record
ord-4c6dd6db2a7d4ec79cb6bb76c0f282b9
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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