Hydroxylamine → 3-([1,1'-biphenyl]-4-ylsulfonyl)-N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide

HRID 1964806Notes

Reaction equation

HRID 1964806 reaction equation
NO.[C:3]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:16][CH2:15][S:14][CH:13]2[C:17]([NH:19][CH:20]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:21][CH2:22]O)=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[C:36]([NH2:47])(=[O:46])[C:37]1[C:38](=[CH:42][CH:43]=[CH:44][CH:45]=1)[C:39](N)=[O:40].CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:3]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:16][CH2:15][S:14][CH:13]2[C:17]([NH:19][CH:20]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:21][CH2:22][N:47]2[C:36](=[O:46])[C:37]3[C:38](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:39]2=[O:40])=[O:18])(=[O:11])=[O:10])=[CH:5][CH:4]=1

Participants

7

Reactant 5

HCID 787HydroxylamineHCID 6956PhthalamideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 103110413-([1,1'-biphenyl]-4-ylsulfonyl)-N-(3-hydroxy-1-phenylpropyl)-1,3-thiazolidine-2-carboxamide

Product 1

HCID 686220633-([1,1'-biphenyl]-4-ylsulfonyl)-N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-phenylpropyl]-1,3-thiazolidine-2-carboxamideYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Intermediates of general structure (XXVI), e.g., 3-([1,1′-biphenyl]-4-ylsulfonyl)-N-(3-hydroxy-1-phenylpropyl)-1,3-thiazolidine-2-carboxamide (1.0 g, 1.0 eq, 2.07 mmol) were dissolved in 20 ml dry THF under nitrogen. Phthalamide (395 mg, 1.5 eq, 2.69 mmol), diethylazodicarboxylate (470 mg, 1.5 eq, 2.69 mmol) and polymer bound triphenyl phosphine (1.0 g, 1.5 eq, 2.70 mmol) were then added and the reaction mixture was shaken for 12 hours at RT. The triphenyl phosphine resin was filtered off and the THF solution evaporated in vacuo. The residue was taken up in DCM and washed twice with a saturated sodium carbonate solution and then water. The organic layer was dried with magnesium sulfate and concentrated in vacuo to give a crude product which was purified on silica gel using cyclohexane/ethyl acetate(7/3) as eluent, to obtain the desired products, e.g., 3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide in 57% yield as a white oil in 96% purity by HPLC.

Workup

  1. filtrationThe triphenyl phosphine resin was filtered off
  2. customthe THF solution evaporated in vacuo
  3. washwashed twice with a saturated sodium carbonate solution
  4. dry with materialThe organic layer was dried with magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a crude product which
  7. customwas purified on silica gel

Sources & evidence

ORD record
ord-3432980b43064ca8a5b47d844669a828
Source dataset
uspto-grants-2013_04
Patent number
US08415480B2

Reaction notes

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