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

HRID 528669ノート

反応式

HRID 528669 の反応式
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

参加物

8

反応物 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 247097994-(2-Bromophenoxy)pyridineHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2 回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

生成物 1

HCID 89762106HCID 89762106、化合物収率 38.4%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)

後処理

  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

出典と根拠

ORDレコード
ord-48a53415ecda4f30a008b9a4a7562ef5
出典データセット
uspto-grants-2016_05
特許番号
US09346798B2

反応ノート

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