Pyrrolidine → 2-[4-((11S,11aS)-7,8-Dimethoxy-11-hydroxy-5-oxo-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyloxymethyl)-phenoxycarbonylamino]-pentanedioic acid

HRID 33995Notes

Reaction equation

HRID 33995 reaction equation
C([O:4][C:5](=[O:49])[CH:6]([NH:15][C:16]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][O:26][C:27]([N:29]2[C:35]3[CH:36]=[C:37]([O:42][CH3:43])[C:38]([O:40][CH3:41])=[CH:39][C:34]=3[C:33](=[O:44])[N:32]3[CH2:45][CH2:46][CH2:47][C@H:31]3[C@@H:30]2[OH:48])=[O:28])=[CH:21][CH:20]=1)=[O:17])[CH2:7][CH2:8][C:9]([O:11]CC=C)=[O:10])C=C.N1CCCC1>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:41][O:40][C:38]1[C:37]([O:42][CH3:43])=[CH:36][C:35]2[N:29]([C:27]([O:26][CH2:25][C:22]3[CH:21]=[CH:20][C:19]([O:18][C:16]([NH:15][CH:6]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])[C:5]([OH:49])=[O:4])=[O:17])=[CH:24][CH:23]=3)=[O:28])[C@@H:30]([OH:48])[C@@H:31]3[CH2:47][CH2:46][CH2:45][N:32]3[C:33](=[O:44])[C:34]=2[CH:39]=1

Participants

5

Reactant 2

HCID 31268PyrrolidineHCID 692552912-[4-((11S,11aS)-7,8-dimethoxy-11-hydroxy-5-oxo-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyloxymethyl)-phenoxycarbonylamino]-pentanedioic acid diallyl ester

Product 1

HCID 690319812-[4-((11S,11aS)-7,8-Dimethoxy-11-hydroxy-5-oxo-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyloxymethyl)-phenoxycarbonylamino]-pentanedioic acidYield 88%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of the diallyl ester 45 (0.596 g, 0.95 mmol, 1 eq), Pd(PPh3)4 (0.055 g, 0.047 mmol, 0.05 eq) and pyrrolidine (0.34 g, 0.39 mL, 4.7 mmol, 5 eq) in anhydrous CH2Cl2 (18 mL) was stirred at room temperature for 1 h and the solvent removed in vacuo. The residue was washed with EtOAc (3×15 mL), dissolved in MeOH (15 mL) and passed down an IRC 50, weakly acidic, ion exchange column, eluting with MeOH (80 mL). The solvent was removed in vacuo to give the product as a white foam (0.46 g, 88%). 1H NMR (d6 DMSO) δ 7.95 (d, J=6.25 Hz, 1H), 7.33 (d, J=8 Hz, 2H), 7.10 (m, 3H) 6.73 (s, 1H), 5. 49 (d, J=9.2 Hz, 1H), 5.2 (d, J=12.5 Hz, 1H), 4.89 (d, J=12.75 Hz, 1H), 4.00 (m, 1H), 3.80 (m, 7H), 3.45 (m, 4H) 2.30 (t, J=7.5 Hz, 2H), 1.95 (m, 5H). MS (ES+) 602.2.

Workup

  1. customthe solvent removed in vacuo
  2. washThe residue was washed with EtOAc (3×15 mL)
  3. dissolutiondissolved in MeOH (15 mL)
  4. washweakly acidic, ion exchange column, eluting with MeOH (80 mL)
  5. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ca92106cd02a42e6852eae3392adf4e6
Source dataset
uspto-grants-2008_09
Patent number
US07429658B2

Reaction notes

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