Diisopropylethylamine → 3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)benzonitrile

HRID 510996노트

반응식

HRID 510996 반응식
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.CCN(C(C)C)C(C)C.[NH2:26][CH:27]([C:29]1[CH:36]=[C:35]([CH3:37])[C:32]([C:33]#[N:34])=[C:31]([C:38]2[CH:39]=[N:40][CH:41]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[CH:43]=2)[C:30]=1[O:48][CH2:49][CH3:50])[CH3:28]>C(O)C>[CH2:49]([O:48][C:30]1[C:31]([C:38]2[CH:39]=[N:40][CH:41]=[C:42]([S:44]([CH3:47])(=[O:45])=[O:46])[CH:43]=2)=[C:32]([C:35]([CH3:37])=[CH:36][C:29]=1[CH:27]([NH:26][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH3:28])[C:33]#[N:34])[CH3:50]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 866669104-(1-Aminoethyl)-3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrile

생성물 1

HCID 866669113-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)benzonitrile

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
120 °C

실험 절차

6-Chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (35 mg, 0.15 mmol, from Example 176, Step 4) and DIPEA (0.04 mL, 0.2 mmol) were added to 4-(1-aminoethyl)-3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]benzonitrile in ethanol (2 mL). The reaction was heated to 120° C. overnight. The reaction was allowed to cool to room temperature and was concentrated in vacuo to give 3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-(1-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]amino}ethyl)benzonitrile as a solid residue. This intermediate was dissolved in 4.0 M HCl in dioxane (1 mL) and was stirred for 10 minutes. The reaction was concentrated and was purified on prep HPLC on a C-18 column eluting with water:acetonitrile gradient buffered with TFA to give 3-ethoxy-6-methyl-2-[5-(methylsulfonyl)pyridin-3-yl]-4-[1-(9H-purin-6-ylamino)ethyl]benzonitrile as a white solid (0.010 g, 16%). LCMS calculated for C23H24N7O3S (M+H)+: m/z=478.1. found: 478.1. 1H NMR (300 MHz, DMSO-d6) δ 9.18 (d, J=2.2 Hz, 1H), 9.09 (d, J=2.0 Hz, 1H), 8.75 (m, 1H), 8.54 (t, J=2.1 Hz, 1H), 8.33 (m, 2H), 7.68 (s, 1H), 5.80 (m, 1H), 3.99-3.79 (m, 1H), 3.40 (s, 3H), 3.34 (m, 1H), 2.47 (s, 3H), 1.58 (d, J=6.9 Hz, 3H), 0.98 (t, J=6.9 Hz, 3H).

후처리

  1. temperatureto cool to room temperature
  2. concentrationwas concentrated in vacuo

출처 및 근거

ORD 기록
ord-e13925490eab497c8e0e0db5b16df083
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096600B2

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