Hydrochloric Acid → Pemetrexed acid

HRID 263706Notes

Reaction equation

HRID 263706 reaction equation
C[O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]2[C:20]3[C:19](=[O:21])[NH:18][C:17]([NH2:22])=[N:16][C:15]=3[NH:14][CH:13]=2)=[CH:6][CH:5]=1.CO.O1CCCC1.Cl>[OH-].[Na+]>[NH2:22][C:17]1[NH:18][C:19](=[O:21])[C:20]2[C:12]([CH2:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:23])=[O:2])=[CH:5][CH:6]=3)=[CH:13][NH:14][C:15]=2[N:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 8028TetrahydrofuranHCID 135471769Methyl 4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate

Product 1

HCID 135405776Pemetrexed acidYield 87.5%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 3.17 g (10.15 mmol) of 4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-5-yl) ethyl]benzoic acid methyl ester, prepared in Example 3, in 30 ml of 1N aqueous sodium hydroxide and 5 ml methanol was stirred for 20 hours at room temperature. Tetrahydrofuran (5 ml) was added and the mixture was stirred for 4 hours then neutralized with 30 ml of 1N aqueous hydrochloric acid. The resulting precipitate was separated by filtration, washed with water (20 ml) and dried in a vacuum oven at 50° C. to obtain 2.65 g of the above product in a yield of 87 percent. 1H NMR (DMSO-d6) δ2.45 (m, 2H), 2.91 (m, 2H), 5.99 (s, 2H), 6.27 (d, J=2.0 Hz, 1H), 7.27 (d, J=8.2 Hz, 2H), 7.79 (d, J=8.2 Hz, 2H), 10.14 (s, 1H), 10.59 (d, J=2.0 Hz, 1H), 13.2 (bs, 1H).

Workup

  1. customThe resulting precipitate was separated by filtration
  2. washwashed with water (20 ml)
  3. customdried in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-042f2106867347f2bf143ae9b86ed290
Source dataset
uspto-grants-1997_07
Patent number
US05644058

Reaction notes

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