1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 89761842, compound

HRID 528670Notes

Reaction equation

HRID 528670 reaction equation
Br[C:2]1[CH:13]=[CH:12][CH:11]=[CH:10][C:3]=1[O:4][C:5]([CH3:9])([CH3:8])[C:6]#[N:7].[CH3:14][O:15][C:16]1[CH:41]=[CH:40][C:19]([CH2:20][N:21]([C:35]2[S:36][CH:37]=[CH:38][N:39]=2)[S:22]([C:25]2[CH:26]=[CH:27][C:28]3[NH:33][CH2:32][CH2:31][O:30][C:29]=3[CH:34]=2)(=[O:24])=[O:23])=[CH:18][CH:17]=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>[C:6]([C:5]([O:4][C:3]1[CH:10]=[CH:11][CH:12]=[CH:13][C:2]=1[N:33]1[CH2:32][CH2:31][O:30][C:29]2[CH:34]=[C:25]([S:22]([N:21]([CH2:20][C:19]3[CH:40]=[CH:41][C:16]([O:15][CH3:14])=[CH:17][CH:18]=3)[C:35]3[S:36][CH:37]=[CH:38][N:39]=3)(=[O:23])=[O:24])[CH:26]=[CH:27][C:28]1=2)([CH3:9])[CH3:8])#[N:7]

Participants

8

Reactant 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 89761362HCID 89761362, compoundHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2×HCID 89761781N-(3-bromo-1,2,4-thiadiazol-5-yl)-4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 89761842HCID 89761842, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A microwave vial containing a suspension of 2-(2-bromophenoxy)-2-methylpropanenitrile (0.173 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 (9.58 ml) was purged with nitrogen and was microwave irradiated at 110° C. for 30 min. Reaction mixture was diluted with EtOAc (50 mL) and washed with saturated NaCl solution. Organic layer was 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 4-(2-((2-cyanopropan-2-yl)oxy)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (44 mg, 0.076 mmol, 16% yield). To the material was then added DCM (1 mL) and TFA (4 drops) and stirred at ambient temperature for 2 h The reaction mixture was 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 4-(2-((2-cyanopropan-2-yl)oxy)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (3.8 mg, 0.008 mmol, 1.6% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.43 (dd, J=8.12, 1.28 Hz, 1 H) 7.39 (dd, J=7.85, 1.55 Hz, 1 H) 7.31-7.37 (m, 1 H) 7.21-7.27 (m, 1 H) 7.11-7.14 (m, 2 H) 7.08 (dd, J=8.55, 2.14 Hz, 1 H) 6.66 (d, J=4.38 Hz, 1 H) 6.34 (d, J=8.44 Hz, 1 H) 5.75 (s, 1 H) 4.26-4.32 (m, 2 H) 3.60-3.65 (m, 2 H) 1.55 (br. s., 6 H); MS (ESI, positive ion) m/z; 457.0 (M+1)

Workup

  1. additionA microwave vial containing
  2. customwas purged with nitrogen
  3. customirradiated at 110° C. for 30 min
  4. customReaction mixture
  5. washwashed with saturated NaCl solution
  6. concentrationOrganic layer was concentrated
  7. custompurified by preperative LC/MS-2 System Column

Sources & evidence

ORD record
ord-5e4dc4c15ad443f1aec71575ebdabc3c
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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