1,1,1-trimethyl-N-((trimethylsilyl)oxy)silylamine → N-((S)-3-(1H-indol-3-yl)-1-(3-(isoquinolin-6-yl)isoxazol-5-ylamino)propan-2-yl)-4-nitrobenzenesulfonamide

HRID 598855Notes

Reaction equation

HRID 598855 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C@H:11]([NH:35][S:36]([C:39]2[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=2)(=[O:38])=[O:37])[CH2:12][N:13]([C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:26]=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH:31]=[N:30][CH:29]=[CH:28]4)[CH:21]=2)C(=O)OCC=C)=[CH:2]1.C[Si](C)(C)NO[Si](C)(C)C>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>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C@H:11]([NH:35][S:36]([C:39]2[CH:40]=[CH:41][C:42]([N+:45]([O-:47])=[O:46])=[CH:43][CH:44]=2)(=[O:37])=[O:38])[CH2:12][NH:13][C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:26]=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH:31]=[N:30][CH:29]=[CH:28]4)[CH:21]=2)=[CH:2]1

Participants

5

Reactant 2

HCID 898151,1,1-trimethyl-N-((trimethylsilyl)oxy)silylamineHCID 67062570HCID 67062570, compound

Product 1

HCID 67062590N-((S)-3-(1H-indol-3-yl)-1-(3-(isoquinolin-6-yl)isoxazol-5-ylamino)propan-2-yl)-4-nitrobenzenesulfonamideYield 86.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of allyl(S)-3-(1H-indol-3-yl)-2-(4-nitrophenylsulfonamido)propyl(3-(isoquinolin-6-yl)isoxazol-5-yl)carbamate (100 mg, 153 μmol) in 2.5 mL of DCM was added Pd(PPh3)4 (5.3 mg, 4.6 μmol) and N,O-bis(trimethylsilyl)hydroxylamine (27 mg, 153 μmol). The mixture was stirred for 15 minutes and was then quenched with 2.5 mL saturated aqueous NH4Cl and the biphasic mixture was stirred for 2 hours. The mixture was then partitioned and the aqueous portion was extracted twice with DCM. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative LC to give N-((S)-3-(1H-indol-3-yl)-1-(3-(isoquinolin-6-yl)isoxazol-5-ylamino)propan-2-yl)-4-nitrobenzenesulfonamide (75 mg, 86% yield). MS m/z: 569 (M+1).

Workup

  1. customwas then quenched with 2.5 mL saturated aqueous NH4Cl
  2. stirringthe biphasic mixture was stirred for 2 hours
  3. customThe mixture was then partitioned
  4. extractionthe aqueous portion was extracted twice with DCM
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative LC

Sources & evidence

ORD record
ord-716ab312ebf94defb21729ae7ad86230
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

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