L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, 1,5-diethyl ester, 4-methylbenzenesulfonate (1:1) → (2S)-2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioic acid

HRID 469266Notes

Reaction equation

HRID 469266 reaction equation
[CH:1]1[C:6]([CH2:7][CH2:8][C:9]2[C:13]3[C:14]([N:16]=[C:17]([NH2:19])[NH:18][C:12]=3[NH:11][CH:10]=2)=[O:15])=[CH:5][CH:4]=[C:3]([C:20]([NH:22][C@H:23]([C:29]([O-:31])=[O:30])[CH2:24][CH2:25][C:26]([O-:28])=[O:27])=[O:21])[CH:2]=1.O.O.O.O.O.O.O.[Na+].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OC(=O)[C@H](CCC(OCC)=O)NC(=O)C1C=CC(CCC2C3C(=O)NC(N)=NC=3NC=2)=CC=1)C>>[NH2:19][C:17]1[NH:18][C:12]2[NH:11][CH:10]=[C:9]([CH2:8][CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:20]([NH:22][C@H:23]([C:29]([OH:31])=[O:30])[CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:21])=[CH:2][CH:1]=3)[C:13]=2[C:14](=[O:15])[N:16]=1

Participants

3

Reactant 2

HCID 135741210L-Glutamic acid, N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-, 1,5-diethyl ester, 4-methylbenzenesulfonate (1:1)HCID 178508846HCID 178508846, compound

Product 1

HCID 178508842(2S)-2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioic acid

Procedure

U.S. Pat. No. 7,138,521 discloses crystalline pemetrexed disodium heptahydrate. This heptahydrate form is prepared from N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]L-glutamic acid diethylester p-toluenesulfonic acid salt, which is saponified at a pH of between 2.5 to 3.5 to give N-[4-[2(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (“pemetrexed diacid”), of the following Formula II:

Sources & evidence

ORD record
ord-6631f91dcc104b3798bf86a54cf99a5b
Source dataset
uspto-grants-2014_01
Patent number
US08629152B2

Reaction notes

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