Potassium Carbonate → tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate

HRID 634156노트

반응식

HRID 634156 반응식
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([C:13]3[C:21]4[C:16](=[CH:17][CH:18]=[C:19](B5OC(C)(C)C(C)(C)O5)[CH:20]=4)[N:15]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:14]=3)[CH:10]=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Br[C:39]1[S:40][C:41]([S:44][CH3:45])=[N:42][N:43]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:45][S:44][C:41]1[S:40][C:39]([C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][CH:18]=2)[N:15]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:14]=[C:13]3[C:11]2[CH:10]=[CH:9][CH:8]=[C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[N:12]=2)=[N:43][N:42]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 222696212-Bromo-5-(methylsulfanyl)-1,3,4-thiadiazoleHCID 68328848tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate

생성물 1

HCID 68327982tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate수율 47.1%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
100 °C

실험 절차

A glass microwave reaction vessel was charged with tert-butyl 3-(6-morpholinopyridin-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (1.20 g, 2.374 mmol) and 2-bromo-5-(methylthio)-1,3,4-thiadiazole (1.002 g, 4.75 mmol) in p-dioxane/H2O (4:1, 15 mL) followed by potassium carbonate (0.984 g, 7.12 mmol, Aldrich) and Pd(PPh3)4 (0.137 g, 0.119 mmol, Strem). The reaction was stirred and heated in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 2 h. The mixture was diluted with DCM (150 mL) and washed with H2O. The organic layer was dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-18% EtOAc in DCM) to give tert-butyl 5-(5-(methylthio)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate (570 mg, 1.118 mmol, 47.1%) as a yellow solid. MS (ESI, pos. ion) m/z: 510 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 8.91 (1H, s), 8.17-8.32 (2H, m), 7.98 (1H, dd, J=8.7, 1.7 Hz), 7.65 (1H, t, J=8.0 Hz), 7.18 (1H, d, J=7.4 Hz), 6.70 (1H, d, J=8.4 Hz), 3.92-4.01 (4H, m), 3.68-3.77 (4H, m), 2.84 (3H, s), 1.72 (9H, s).

후처리

  1. customA glass microwave reaction vessel
  2. washwashed with H2O
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 0-18% EtOAc in DCM)

출처 및 근거

ORD 기록
ord-72731119dab5465da98cdbfbe1a87e2d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321756B2

반응 노트

불러오는 중…