p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamate → (S)-3-benzyloxycarbonylamino-N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acid

HRID 459771

Reaction equation

HRID 459771 reaction equation
C([O:8][C:9](=[O:45])[CH2:10][C@H:11]([NH:34][C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36])[C:12]([NH:14][C:15]1[CH:20]=[C:19]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[NH:24][N:23]=2)[CH:18]=[CH:17][C:16]=1[F:33])=[O:13])C1C=CC=CC=1.CC1C=CC(COC(NNC(C2C=NC=CN=2)=O)=O)=CC=1>C(=O)([O-])[O-].[Na+].[Na+]>[CH2:38]([O:37][C:35]([NH:34][C@H:11]([C:12]([NH:14][C:15]1[CH:20]=[C:19]([CH2:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](=[O:32])[NH:24][N:23]=2)[CH:18]=[CH:17][C:16]=1[F:33])=[O:13])[CH2:10][C:9]([OH:45])=[O:8])=[O:36])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

4

Reactant 2

HCID 478568p-tolylmethyl N-(pyrazine-2-carbonylamino)carbamateHCID 58823934(S)-3-benzyloxycarbonylamino-N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acid benzyl ester

Product 1

HCID 58823962(S)-3-benzyloxycarbonylamino-N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acidYield 72.1%

Reagents, catalysts & solvents 1

HCID 10340Sodium CarbonateSolvent2×

Procedure

A mixture of the above crude (S)-3-benzyloxycarbonylamino-N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acid benzyl ester (0.57 g) and saturated aqueous sodium carbonate solution (pH 9; 10 ml) was stirred at ambient temperature for 72 hours. The pH of the mixture was adjusted to pH10 by the addition of further saturated aqueous sodium carbonate solution, then the mixture was stirred at 70° C. for 4 hours until a clear solution was obtained. The cooled solution was washed with ethyl acetate (2×5 ml) and the aqueous layer was acidified by the addition of 10% hydrochloric acid. The resulting solid was collected by filtration and dried in vacuo to give (S)-3-benzyloxycarbonylamino-N-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]succinamic acid (0.35 g) as an off-white solid, m.pt. 188–190° C., which was used without further purification.

Workup

  1. stirringthe mixture was stirred at 70° C. for 4 hours until a clear solution
  2. customwas obtained
  3. washThe cooled solution was washed with ethyl acetate (2×5 ml)
  4. additionthe aqueous layer was acidified by the addition of 10% hydrochloric acid
  5. filtrationThe resulting solid was collected by filtration
  6. customdried in vacuo

Sources & evidence

ORD record
ord-65844b9017ad46ad93088862246c8dc2
Source dataset
uspto-grants-2007_03
Patent number
US07196085B2

Linked notes

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