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 1400815ノート

反応式

HRID 1400815 の反応式
[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

参加物

7

反応物 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

生成物 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-ylcarbamate収率 82.4%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-d6121d112d2a4862a047346424c19661
出典データセット
uspto-grants-2014_12
特許番号
US08906852B2

反応ノート

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