Pyrrolidine → 6,6-Dimethyl-2-{6-[(6-(pyrrolidin-1-yl)pyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

HRID 885988

반응식

HRID 885988 반응식
Br[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]3[O:17][CH2:16][CH2:15][N:14]([C:18]4[S:19][C:20]5[C:21](=[O:29])[NH:22][C:23]([CH3:28])([CH3:27])[CH2:24][C:25]=5[N:26]=4)[C:13]=3[CH:30]=2)[CH:5]=[CH:4][CH:3]=1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.CC(P(C(C)(C)C)C1[CH-]C=CC=1)(C)C.[Cl-].[Cl-].[Fe+2].[Pd+2]>[CH3:27][C:23]1([CH3:28])[NH:22][C:21](=[O:29])[C:20]2[S:19][C:18]([N:14]3[C:13]4[CH:30]=[C:9]([O:8][C:6]5[CH:5]=[CH:4][CH:3]=[C:2]([N:31]6[CH2:35][CH2:34][CH2:33][CH2:32]6)[N:7]=5)[CH:10]=[CH:11][C:12]=4[O:17][CH2:16][CH2:15]3)=[N:26][C:25]=2[CH2:24]1

참가 물질

6

반응물 3

HCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 873022572-{6-[(6-Bromopyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,6-dimethyl-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one

생성물 1

HCID 685970836,6-Dimethyl-2-{6-[(6-(pyrrolidin-1-yl)pyridin-2-yl)oxy]-2,3-dihydro-4h-1,4-benzoxazin-4-yl}-6,7-dihydro[1,3]thiazolo[5,4-c]pyridin-4(5h)-one수율 35%

시약·촉매·용매 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)촉매HCID 1140Toluene용매

반응 조건

온도
140 °C

실험 절차

To a suspension of Example 382 (50 mg, 0.103 mmol) in toluene (4 mL) was added pyrrolidine (0.025 ml, 0.308 mmol), sodium tert-butoxide (20 mg, 0.206 mmol) and [1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (10 mg, 20% wt). The reaction was heated to 140° C. under microwave irradiation for 90 minutes then cooled to room temperature. The mixture was partitioned between DCM (50 mL) and water (50 mL); the organic phase was washed with brine (50 mL), dried (MgSO4), and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (17 mg, 35%) as an off-white solid. δH (CDCl3) 7.91 (1H, d, J 2.4 Hz), 7.39 (1H, t, J 7.9 Hz), 6.93 (1H, d, J 8.9 Hz), 6.88 (1H, dd, J 8.9 and 2.4 Hz), 6.02 (1H, d, J 8.1 Hz), 5.91 (1H, d, J 7.7 Hz), 5.29 (1H, s), 4.38-4.29 (2H, m), 4.15-4.06 (2H, m), 3.45-3.37 (4H, m), 2.85 (2H, s), 2.01-1.92 (4H, m), 1.37 (6H, s). LCMS (ES+) 478.0 (M+H)+, RT 3.96 minutes (Method 1).

후처리

  1. temperaturethen cooled to room temperature
  2. customThe mixture was partitioned between DCM (50 mL) and water (50 mL)
  3. washthe organic phase was washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative HPLC (Method 6)

출처 및 근거

ORD 기록
ord-844457968e2547dfba3990918931a85f
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242116B2

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