Sodium bis(trimethylsilyl)amide → N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide

HRID 1812371

반응식

HRID 1812371 반응식
F[C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH3:9])=[CH:4][C:3]=1[C:16]1[N:24]=[C:23]([CH3:25])[N:22]=[C:21]2[C:17]=1[N:18]=[CH:19][N:20]2[CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][O:27]1.[NH2:32][C:33]1[CH:34]=[C:35]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])[C:36]([Cl:39])=[N:37][CH:38]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Cl:39][C:36]1[C:35]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])=[CH:34][C:33]([NH:32][C:2]2[C:3]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][N:20]4[CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)=[CH:4][C:5]([CH:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[CH3:9])=[CH:6][N:7]=2)=[CH:38][N:37]=1

참가 물질

5

반응물 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 665998534-(1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)morpholineHCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

생성물 1

HCID 86647079N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide수율 73.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

To a stirred solution of 4-(1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)morpholine (0.157 g, 0.368 mmol) and N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (Example 330 step 2, 0.103 g, 0.462 mmol) in THF (2 mL) in 20 mL microwave vial, NaHMDS (Aldrich, 1 M in THF, 1.47 mL, 1.47 mmol) was added dropwise at 0° C. The dark red mixture was stirred at 0° C. for 30 min. The mixture was partitioned between a mixture of saturated aqueous sodium chloride (10 mL)/buffer (pH 5.0, citric acid/NaOH) (10 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (50 g, eluent: iPrOH in CHCl3 0% to 10%) to afford N-(2-chloro-5-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-morpholinoethyl)pyridin-2-ylamino)pyridin-3-yl)methanesulfonamide (0.169 g, 73% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 13.18 (s, 1H) 9.78 (d, J=1.96 Hz, 1H) 8.83 (d, J=2.54 Hz, 1H) 8.63 (d, J=2.54 Hz, 1H) 8.36 (d, J=2.35 Hz, 1H) 8.31 (s, 1H) 6.76 (br. s., 1H) 5.85-5.90 (m, 1H) 4.17-4.24 (m, 1H) 3.79-3.88 (m, 1H) 3.73 (t, J=4.50 Hz, 4H) 3.51-3.59 (m, 1H) 3.14 (s, 3H) 2.94 (s, 3H) 2.45-2.62 (m, 4H) 2.01-2.22 (m, 3H) 1.66-1.93 (m, 3H) 1.48 (d, J=6.65 Hz, 3H). m/z (ESI, positive ion): 628.0 (M+H)+.

후처리

  1. customThe mixture was partitioned between a mixture of saturated aqueous sodium chloride (10 mL)/buffer (pH 5.0, citric acid/NaOH) (10 mL) and EtOAc (20 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel column chromatography (50 g, eluent: iPrOH in CHCl3 0% to 10%)

출처 및 근거

ORD 기록
ord-bbe0f82100bc42e3aa2c41183cce3336
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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