1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N-(4-methoxybenzyl)-4-(2-(tetrahydro-2H-pyran-4-yl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528581

Reaction equation

HRID 528581 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.I[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[N:20]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 897614262-(4-Tetrahydropyranyl)iodobenzeneHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 89761933N-(4-methoxybenzyl)-4-(2-(tetrahydro-2H-pyran-4-yl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

A microwave vial was charged N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.120 g, 0.287 μmol), 4-(2-iodophenyl)tetrahydro-2H-pyran (0.124 g, 0.431 μmol), sodium tert-butoxide (0.055 g, 0.575 μmol), tris(dibenzylideneacetone)dipalladium(0) (0.026 g, 0.029 μmol) and xantphos (0.033 g, 0.057 μmol). After purging with N2, toluene (3 mL) was added and the vessel was sealed and heated in the microwave at 130° C. for 30 min. LCMS confirmed coupling product formation. The reaction mixture was concentrated and taken up in DCM, then passed through a 12 g silica gel plug, eluting with 1:1 EtOAC/hex to afford N-(4-methoxybenzyl)-4-(2-(tetrahydro-2H-pyran-4-yl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as a semi-pure orange solid.

Workup

  1. customAfter purging with N2, toluene (3 mL)
  2. additionwas added
  3. customthe vessel was sealed
  4. concentrationThe reaction mixture was concentrated
  5. washeluting with 1:1 EtOAC/hex

Sources & evidence

ORD record
ord-252bf7dde8ae4795a3a3d19789773b2d
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Linked notes

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