Triethylamine → (S)-tert-butyl 1-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1400815노트

반응식

HRID 1400815 반응식
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]6[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.[C:38]([NH:45][C@H:46]([C:50](O)=[O:51])[CH:47]([CH3:49])[CH3:48])([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39].C(N(CC)CC)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][C:27]([CH2:30][N:31]6[CH2:32][CH2:33][N:34]([C:50](=[O:51])[C@@H:46]([NH:45][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH:47]([CH3:49])[CH3:48])[CH2:35][CH2:36]6)=[CH:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)[CH2:3][CH2:2]1

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 83693Boc-L-ValineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 674423881-Cyclopropyl-3-(3-fluoro-4-(2-(5-(piperazin-1-ylmethyl)pyridin-2-yl)thieno[3,2-b]-pyridin-7-yloxy)phenyl)urea

생성물 1

HCID 67442183(S)-tert-butyl 1-(4-((6-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)piperazin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate수율 82.4%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred solution of compound 49 (150 mg, 0.289 mmol, scheme 15), Boc-L-valine (94 mg, 0.43 mmol) and triethylamine (120 μL, 0.87 mmol) in DMF (5 mL) under nitrogen were added HOBT monohydrate (49 mg, 0.32 mmol) and EDC hydrochloride (139 mg, 0.72 mmol) reagents, and the reaction mixture was stirred at RT overnight. The reaction mixture was then partitioned between AcOEt and a saturated aqueous solution of sodium bicarbonate. The organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of ammonium chloride and brine, dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product was purified by Biotage (Snap 25 g; MeOH/DCM: 1/99 to 10/90 over 20 CV), to afford the title compound 75 (171 mg, 0.238 mmol, 82% yield) as a colorless sticky film. MS (m/z): 718.4 (M+H).

후처리

  1. customThe reaction mixture was then partitioned between AcOEt
  2. washThe organic layer was successively washed with a saturated aqueous solution of sodium bicarbonate
  3. dry with materiala saturated aqueous solution of ammonium chloride and brine, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by Biotage (Snap 25 g; MeOH/DCM: 1/99 to 10/90 over 20 CV)

출처 및 근거

ORD 기록
ord-d6121d112d2a4862a047346424c19661
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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