1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile

HRID 528609노트

반응식

HRID 528609 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][NH:7][C:6]=2[CH:11]=1.Br[C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=1[O:21][CH3:22].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>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:13]3[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][C:14]=3[O:21][CH3:22])[C:6]=2[CH:11]=1

참가 물질

7

반응물 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 162444596-Fluoro-3,4-dihydro-2H-1,4-benzoxazineHCID 225911814-Bromo-3-methoxybenzonitrileHCID 23676156Sodium t-butoxideHCID 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

생성물 1

HCID 897619874-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile수율 92%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

To a 10-20 ml microwave vial charged with 6-fluoro-3,4-dihydro-2h-benzo[1,4]oxazine (Ark Pharm) (0.150 g, 0.979 mmol), 4-bromo-3-methoxybenzonitrile (Combi-Blocks) (0.312 g, 1.469 mmol), and sodium t-butoxide (0.240 ml, 1.959 mmol) was added Toluene (9.79 ml). The mixture was purged with argon prior to the additions of xantphos (0.113 g, 0.196 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.090 g, 0.098 mmol). The mixture was irradiated at 110° C. for 30 min. The resulting dark suspension was filtered through celite and the filtrate dried under reduced pressure and purified with a 50 g SNAP column ramping EtOAc in heptane (0-40%, 10% DCM throughout) providing product as a light brown foam 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile (0.255 g, 0.897 mmol, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.58-3.65 (m, 2 H) 4.19-4.26 (m, 2 H) 6.07 (dd, J=10.95, 2.93 Hz, 1 H) 6.47 (td, J=8.51, 2.93 Hz, 1 H) 6.79 (dd, J=8.80, 5.58 Hz, 1 H) 7.41-7.45 (m, 1 H) 7.45-7.51 (m, 1 H) 7.62 (d, J=1.66 Hz, 1 H). m/z (ESI) 285.2 (M+H)+.

후처리

  1. customThe mixture was purged with argon
  2. customThe mixture was irradiated at 110° C. for 30 min
  3. filtrationThe resulting dark suspension was filtered through celite
  4. customthe filtrate dried under reduced pressure
  5. custompurified with a 50 g SNAP column

출처 및 근거

ORD 기록
ord-a828e27264804483be3e688218d740e9
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346798B2

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