Potassium Phosphate, Tribasic → N-(4-methoxybenzyl)-4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528542

반응식

HRID 528542 반응식
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[CH2:17][CH2:16][O:15][C:14]2[CH:18]=[C:19]([S:22]([N:25]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=3)[C:26]3[S:27][CH:28]=[CH:29][N:30]=3)(=[O:24])=[O:23])[CH:20]=[CH:21][C:13]1=2.[CH3:40][N:41]1[C:45](B2OC(C)(C)C(C)(C)O2)=[CH:44][CH:43]=[N:42]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C>[CH3:39][O:38][C:35]1[CH:34]=[CH:33][C:32]([CH2:31][N:25]([C:26]2[S:27][CH:28]=[CH:29][N:30]=2)[S:22]([C:19]2[CH:20]=[CH:21][C:13]3[N:12]([C:3]4[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:11])[F:10])=[CH:7][C:2]=4[C:45]4[N:41]([CH3:40])[N:42]=[CH:43][CH:44]=4)[CH2:17][CH2:16][O:15][C:14]=3[CH:18]=2)(=[O:24])=[O:23])=[CH:37][CH:36]=1

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 897617974-(2-chloro-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2회

생성물 1

HCID 89762089N-(4-methoxybenzyl)-4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

시약·촉매·용매 1

HCID 178482226HCID 178482226, 화합물촉매

반응 조건

온도
112 °C

실험 절차

A 5-mL glass microwave reaction vessel was charged with 4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE X, 0.150 g, 0.252 mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (0.131 g, 0.629 mmol), 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(II) chloride (0.027 g, 0.038 mmol), and potassium phosphate (0.083 mL, 1.007 mmol). The vial was sealed and flushed with N2 and dioxane (1 mL) and water (0.32 mL) were added. The mixture was sparged with N2 for 5 min and heated microwave reactor at 112° C. for 3 h. The mixture was diluted with EtOAc and the organic layer was decanted, concentrate and absorbed onto a 5 g loading cartridge and passed through a silica gel column (12 g) using a gradient from 0% to 80% EtOAc in Heptanes to provide N-(4-methoxybenzyl)-4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide. This product was dissolved in DCM (1 mL), cooled to 0° C., and trifluoroacetic acid was added (0.5 mL) dropwise. The solution was maintained at rt for 15 min, then concentrated to dryness. The residue was taken up in DCM and passed through an SCX column (10 g column), flushing with DCM. The product was released by treatment of the SCX column with ammonia (2.0 M) in methanol to afford EXAMPLE 42: 4-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.030 g, 0.058 mmol). 1H NMR (500 MHz, DMSO-d6) δ ppm 3.66 (s, 2 H) 3.90 (s, 4 H) 4.11 (br. s., 1 H) 6.33 (d, J=1.82 Hz, 1 H) 6.49 (s, 1 H) 6.62-6.73 (m, 1 H) 7.05-7.15 (m, 2 H) 7.43 (d, J=1.82 Hz, 1 H) 7.67 (d, J=8.44 Hz, 1 H) 7.80 (s, 1 H) 7.85 (d, J=8.44 Hz, 1 H).

후처리

  1. customThe vial was sealed
  2. customflushed with N2 and dioxane (1 mL) and water (0.32 mL)
  3. additionwere added
  4. customThe mixture was sparged with N2 for 5 min
  5. additionThe mixture was diluted with EtOAc
  6. customthe organic layer was decanted
  7. concentrationconcentrate
  8. customabsorbed onto a 5 g loading cartridge

출처 및 근거

ORD 기록
ord-1e5c198008b641eb9d419317315e7ef6
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346798B2

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