1-Methylimidazole → phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino) carbonyl]-1-pyrazolidinecarboxylate

HRID 1396925Notes

Reaction equation

HRID 1396925 reaction equation
CN1C=CN=C1.[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:14]([N:16]2[C@H:20]([C:21](O)=[O:22])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])=[O:15])[CH2:11][CH2:10][CH2:9][CH2:8]1.S(Cl)(C)(=O)=O.[CH3:51][C@H:52]1[CH2:57][N:56]([CH3:58])[CH2:55][CH2:54][N:53]1[C:59]1[N:64]=[C:63]([NH2:65])[CH:62]=[CH:61][N:60]=1>ClCCl>[CH:7]1([CH2:12][C@H:13]([CH2:34][N:35]([CH:44]=[O:45])[O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:14]([N:16]2[C@H:20]([C:21]([NH:65][C:63]3[CH:62]=[CH:61][N:60]=[C:59]([N:53]4[CH2:54][CH2:55][N:56]([CH3:58])[CH2:57][C@@H:52]4[CH3:51])[N:64]=3)=[O:22])[CH2:19][CH2:18][N:17]2[C:24]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25])=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 31297Methanesulfonyl chlorideHCID 682880252-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinamineHCID 86706346(3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

Product 1

HCID 86706365phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino) carbonyl]-1-pyrazolidinecarboxylateYield 58.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-Methylimidazole (133 μl, 1.674 mmol) was added into the solution of (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (300 mg, 0.558 mmol) in dichloromethane (DCM) (4 ml). The resulting solution was cooled to 0° C., and then mesyl chloride (45.4 μl, 0.586 mmol) was added dropwise at 0° C. To the reaction mixture was added 2-[(25)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinamine (127 mg, 0.614 mmol). After stirring for 1 h 40 min at ambient temperature, the reaction solution was purified by RP-HPLC to yield phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(2S)-2,4-dimethyl-1-piperazinyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidinecarboxylate (236 mg, 0.325 mmol, 58% yield). MS (ES+) m/z 515.4 (MH+). MS (ES+) m/z 727.3 (MH+).

Workup

  1. customthe reaction solution was purified by RP-HPLC

Sources & evidence

ORD record
ord-efc58f90cec74c228f338fae60ad4425
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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