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Dichloromethane → 2-Methyl-propane-2-sulfinic acid (3-{-4-[3,6-dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-phenyl}-oxetan-3-yl)-amide

HRID 1037326
Notes
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Reaction equation

HRID 1037326 reaction equation
I[C:2]1[C:3](=[O:30])[C:4]2[CH:5]=[CH:6][N:7]3[C:20](=[O:21])[N:19]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[N:18]=[C:8]3[C:9]=2[O:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CC1(C)C(C)(C)OB([C:39]2[CH:44]=[CH:43][C:42]([C:45]3([NH:49][S:50]([C:52]([CH3:55])([CH3:54])[CH3:53])=[O:51])[CH2:48][O:47][CH2:46]3)=[CH:41][CH:40]=2)O1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[O:21]=[C:20]1[N:7]2[CH:6]=[CH:5][C:4]3[C:3](=[O:30])[C:2]([C:39]4[CH:40]=[CH:41][C:42]([C:45]5([NH:49][S:50]([C:52]([CH3:55])([CH3:54])[CH3:53])=[O:51])[CH2:48][O:47][CH2:46]5)=[CH:43][CH:44]=4)=[C:11]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[O:10][C:9]=3[C:8]2=[N:18][N:19]1[CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 670678002-Methyl-propane-2-sulfinic acid {3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-phenyl]-oxetan-3-yl}-amideHCID 866710397-Iodo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalene-3,6-dione

Product 1

HCID 86671050
2-Methyl-propane-2-sulfinic acid (3-{-4-[3,6-dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-phenyl}-oxetan-3-yl)-amide
Yield 70%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 7-iodo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalene-3,6-dione (53.5 mg, 0.10 mmol), 2-methyl-propane-2-sulfinic acid {3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-phenyl]-oxetan-3-yl}-amide (57 mg, 0.15 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (4 mg, 0.005 mmol), sodium carbonate solution (2 M in water, 0.3 mL, 0.6 mmol) and DME (2 mL) was purged using nitrogen and heated in a microwave reactor at 125° C. for 1 h. The reaction mixture was allowed to cool to RT and was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 5 (% MeOH in EtOAc) to afford the title compound (46 mg, 70%) as a yellow gum. LCMS (Method H): RT=3.95 min, [M+H]+=661.

Workup

  1. customwas purged
  2. temperatureto cool to RT
  3. customwas partitioned between EtOAc and water
  4. extractionThe aqueous phase was extracted with EtOAc
  5. washthe combined organic extracts were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-30e183dde44a4fdba746da42c531f780
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08546376B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes