1-Methylimidazole → 2-propen-1-yl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-({[5-(methyloxy)-2-pyrimidinyl]amino}carbonyl)-1-pyrazolidinecarboxylate

HRID 1396927Notes

Reaction equation

HRID 1396927 reaction equation
CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:30][N:31]([CH:39]=[O:40])[O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:14]([N:16]2[CH:20]([C:21]([OH:23])=O)[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.S(Cl)(C)(=O)=O.[CH3:46][O:47][C:48]1[CH:49]=[N:50][C:51]([NH2:54])=[N:52][CH:53]=1>ClCCl>[CH:7]1([CH2:12][C@H:13]([CH2:30][N:31]([CH:39]=[O:40])[O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:14]([N:16]2[C@H:20]([C:21]([NH:54][C:51]3[N:52]=[CH:53][C:48]([O:47][CH3:46])=[CH:49][N:50]=3)=[O:23])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][CH:28]=[CH2:29])=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 23052442-Amino-5-methoxypyrimidineHCID 867063582-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-1-[(2-propen-1-yloxy)carbonyl]-3-pyrazolidinecarboxylic acid

Product 1

HCID 867063662-propen-1-yl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-({[5-(methyloxy)-2-pyrimidinyl]amino}carbonyl)-1-pyrazolidinecarboxylateYield 44.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-Methylimidazole (158 μl, 1.987 mmol) was added into the solution of 2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-1-[(2-propen-1-yloxy)carbonyl]-3-pyrazolidinecarboxylic acid (319 mg, 0.662 mmol) in dichloromethane (DCM) (4.5 ml). The resulting solution was cooled to 0° C., and then mesyl chloride (53.8 μl, 0.696 mmol) was added dropwise at 0° C. To the reaction mixture was added 5-(methyloxy)-2-pyrimidinamine (87 mg, 0.696 mmol). After stirring for 30 min at ambient temperature, the solvent was removed under reduced pressure to give a residue which was purified by RP-HPLC to yield 2-propen-1-yl (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoyl)-3-({[5-(methyloxy)-2-pyrimidinyl]amino}carbonyl)-1-pyrazolidinecarboxylate (173 mg, 0.294 mmol, 44% yield). MS (ES+) m/z 589.1 (MH+).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customto give a residue which
  3. customwas purified by RP-HPLC

Sources & evidence

ORD record
ord-aa3a8774b12c4532a88ce3b56203724c
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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