Trifluoroacetic acid → 4-(2-Cyano-4-Methoxyphenyl)-N-(Thiazol-2-Yl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonamide 2,2,2-Trifluoroacetate

HRID 528583

반응식

HRID 528583 반응식
COC1C=CC(C[N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=CC=1.Br[C:30]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:31]=1[C:32]#[N:33].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.CC(C)([O-])C.[Na+].[F:88][C:89]([F:94])([F:93])[C:90]([OH:92])=[O:91]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:88][C:89]([F:94])([F:93])[C:90]([OH:92])=[O:91].[C:32]([C:31]1[CH:34]=[C:35]([O:38][CH3:39])[CH:36]=[CH:37][C:30]=1[N:20]1[CH2:19][CH2:18][O:17][C:16]2[CH:21]=[C:12]([S:9]([NH:8][C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:10])=[O:11])[CH:13]=[CH:14][C:15]1=2)#[N:33]

참가 물질

8

반응물 5

HCID 6422Trifluoroacetic acidHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 217840962-Bromo-5-methoxybenzonitrileHCID 23676156Sodium t-butoxideHCID 89761436N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide2회

생성물 1

HCID 897620254-(2-Cyano-4-Methoxyphenyl)-N-(Thiazol-2-Yl)-3,4-Dihydro-2H-Benzo[B][1,4]Oxazine-7-Sulfonamide 2,2,2-Trifluoroacetate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
130 °C

실험 절차

A microwave vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M, 0.125 g, 0.299 mmol), 2-bromo-5-methoxybenzonitrile (ASDI, 0.111 g, 0.524 mmol), Xantphos (0.035 g, 0.060 mmol), Pd2(dba)3 (0.027 g, 0.030 mmol) and sodium tert-butoxide (0.058 g, 0.599 mmol). The mixture was diluted with Toluene (2.00 ml), and purged with nitrogen, and heated at 130° C. in the microwave for 30 minutes. After cooling to RT, trifluoroacetic acid (0.577 ml, 7.48 mmol) was added to the crude reaction mixture, and the reaction was stirred at RT for 2 h ( ), after which the crude reaction was filtered over a plug of Celite (washing with minimal DCM to flush through the product). The reactions were then dried overnight in a hood and purified using reverse phase mass-directed HPLC. The column used was a Waters Xbridge C18 19×100 mm 10 micron column. The mobile phase was run under gradient conditions using Water and CH3CN with 0.1% trifluoroacetic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1 H) 7.55 (d, J=2.86 Hz, 1 H) 7.51 (d, J=8.94 Hz, 1 H) 7.37 (dd, J=8.94, 2.86 Hz, 1 H) 7.21 (d, J=4.47 Hz, 1 H) 7.16 (d, J=1.83 Hz, 1 H) 7.13 (dd, J=8.48, 1.95 Hz, 1 H) 6.78 (d, J=4.47 Hz, 1 H) 6.29 (d, J=8.59 Hz, 1 H) 4.31-4.37 (m, 2 H) 3.84 (s, 3 H) 3.68-3.73 (m, 2 H). m/z (ESI) 428.1 (M+H)+.

후처리

  1. custompurged with nitrogen
  2. temperatureAfter cooling to RT
  3. customreaction mixture
  4. customreaction
  5. filtrationwas filtered over a plug of Celite (
  6. washwashing with minimal DCM
  7. customto flush through the product)
  8. customThe reactions were then dried overnight in a hood
  9. custompurified

출처 및 근거

ORD 기록
ord-61a1c2c0e85f413eb3beb531c12c4871
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346798B2

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