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

反応式

HRID 885988 の反応式
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

参加物

6

反応物 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

生成物 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)-one収率 35%

試薬・触媒・溶媒 2

HCID 53384307Dichloro[1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II)触媒HCID 1140Toluene溶媒

反応条件

温度
140 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-844457968e2547dfba3990918931a85f
出典データセット
uspto-grants-2012_08
特許番号
US08242116B2

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