Sodium bis(trimethylsilyl)amide → N'-(2-chloro-5-((3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-(4-morpholinyl)ethyl)-2-pyridinyl)amino)-3-pyridinyl)-N,N-dimethylsulfamide

HRID 1621964

반응식

HRID 1621964 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]([N:44]([CH3:46])[CH3:45])(=[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]([N:44]([CH3:45])[CH3:46])(=[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 71480922N'-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide

생성물 1

HCID 86647080N'-(2-chloro-5-((3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-(4-morpholinyl)ethyl)-2-pyridinyl)amino)-3-pyridinyl)-N,N-dimethylsulfamide수율 65%

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 (Example 339 step 4, 0.0475 g, 0.111 mmol) and N′-(5-amino-2-chloro-3-pyridinyl)-N,N-dimethylsulfamide (Example 384, Step 2 0.0380 g, 0.152 mmol) in THF (1 mL) in 20 mL scintillation vial, NaHMDS (Aldrich, 1 M in THF, 0.445 mL, 0.445 mmol) was added dropwise at 0° C. The dark red mixture was stirred at 0° C. for 30 min. The reaction mixture was partitioned between buffer (pH 5.0, citric acid/NaOH) (20 mL) and EtOAc (20 mL) resulted in having insoluble materials. The biphase mixture was filtered and the solid was collected and washed with water to afford N′-(2-chloro-5-((3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-(1-(4-morpholinyl)ethyl)-2-pyridinyl)amino)-3-pyridinyl)-N,N-dimethylsulfamide (0.0472 g, 65% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 13.12 (s, 1H) 9.76 (s, 1H) 8.86 (d, J=2.35 Hz, 1H) 8.50 (d, J=1.96 Hz, 1H) 8.32 (s, 2H) 6.79 (br. s., 1H) 5.87 (d, J=8.22 Hz, 1H) 4.16-4.26 (m, 1H) 3.79-3.90 (m, 1H) 3.73 (br. s., 4H) 3.55 (br. s., 1H) 2.87-3.04 (m, 9H) 2.50 (br. s., 4H) 1.98-2.21 (m, 3H) 1.69-1.92 (m, 3H) 1.48 (d, J=6.46 Hz, 3H). m/z (ESI, positive ion): 657.0 (M+H)+.

후처리

  1. customThe reaction mixture was partitioned between buffer (pH 5.0, citric acid/NaOH) (20 mL) and EtOAc (20 mL)
  2. customresulted
  3. filtrationThe biphase mixture was filtered
  4. customthe solid was collected
  5. washwashed with water

출처 및 근거

ORD 기록
ord-1e702ef548ac47ce9ae5a15f18a974ed
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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