1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 89762106, compound

HRID 528669Notes

Reaction equation

HRID 528669 reaction equation
Br[C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=1.[CH3:15][O:16][C:17]1[CH:42]=[CH:41][C:20]([CH2:21][N:22]([C:36]2[S:37][CH:38]=[CH:39][N:40]=2)[S:23]([C:26]2[CH:27]=[CH:28][C:29]3[NH:34][CH2:33][CH2:32][O:31][C:30]=3[CH:35]=2)(=[O:25])=[O:24])=[CH:19][CH:18]=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.BrC1N=C(N(CC2C=CC(OC)=CC=2)S(C2C=CC3N(C4C=CC(C(F)(F)F)=CC=4Cl)CCOC=3C=2)(=O)=O)SN=1>C1(C)C=CC=CC=1.CCOC(C)=O>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][N:22]([C:36]2[S:37][CH:38]=[CH:39][N:40]=2)[S:23]([C:26]2[CH:27]=[CH:28][C:29]3[N:34]([C:2]4[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=4[O:4][C:5]4[CH:10]=[CH:9][N:8]=[CH:7][CH:6]=4)[CH2:33][CH2:32][O:31][C:30]=3[CH:35]=2)(=[O:25])=[O:24])=[CH:41][CH:42]=1

Participants

8

Reactant 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 24709799HCID 24709799, compoundHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×HCID 89761781HCID 89761781, compound

Product 1

HCID 89762106HCID 89762106, compoundYield 38.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A microwave vial containing a suspension of 4-(2-bromophenoxy)pyridine (0.180 g, 0.719 mmol), N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (Intermediate M; 0.2 g, 0.479 mmol), sodium t-butoxide (0.117 ml, 0.958 mmol), Xantphos (0.111 g, 0.192 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.088 g, 0.096 mmol) in toluene (4.79 ml) was purged with nitrogen and was microwave irradiated at 100° C. for 45 min. Reaction mixture was diluted with EtOAc (100 mL) and washed with water (2×50 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by preperative LC/MS-2 System Column: XBridge 19×100 mm 12230326114 03 Mobile phase: 0.1% NH4OH in water/acetonitrile Flow rate: 40 ml/min Inj: 2200 uL. Gradient: 10 min5-50% shallow; 10 min10-60% shallow to obtain N-(4-methoxybenzyl)-4-(2-(pyridin-4-yloxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.108 g, 0.184 mmol, 38.4% yield) as yellow solid. The material was then dissolved in DCM (1 mL) and TFA was added (1 ml). The reaction mixture was concentrated and purified by MPLC (Biotage Isolera One; PuriFlash HP, 15p., 80 g), eluting with DCM:MeOH (90:10) to obtain 4-(2-(pyridin-4-yloxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.03 g, 0.064 mmol, 13.42% yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1 H) 8.30-8.34 (m, 2 H) 7.50-7.54 (m, 1 H) 7.41-7.45 (m, 2 H) 7.33-7.38 (m, 1 H) 7.23 (d, J=4.60 Hz, 1 H) 7.13 (dd, J=8.51, 2.15 Hz, 1 H) 7.02 (d, J=2.15 Hz, 1 H) 6.79 (d, J=4.60 Hz, 1 H) 6.64-6.68 (m, 2 H) 6.43 (d, J=8.51 Hz, 1 H) 3.56 (br. s., 2 H) 3.29 (br. s., 1H); MS (ESI, positive ion) m/z; 467.1 (M+1)

Workup

  1. additionA microwave vial containing
  2. customwas purged with nitrogen
  3. customirradiated at 100° C. for 45 min
  4. customReaction mixture
  5. washwashed with water (2×50 mL)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. custompurified by preperative LC/MS-2 System Column

Sources & evidence

ORD record
ord-48a53415ecda4f30a008b9a4a7562ef5
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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