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Acetic Acid → 1-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea

HRID 1174869
ノート
印刷プレビュー

反応式

HRID 1174869 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]([NH:13][C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)=[O:15])=[CH:11][C:10]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[Si:34]([O:41][CH2:42][CH2:43][CH:44]=O)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1>[C:30]([C:10]1[CH:11]=[C:12]([NH:13][C:14]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([O:23][C:24]3[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=3)=[CH:21][CH:22]=2)=[O:15])[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][CH2:44][CH2:43][CH2:42][O:41][Si:34]([C:37]([CH3:38])([CH3:40])[CH3:39])([CH3:35])[CH3:36])[CH:3]=2)[N:9]=1)([CH3:33])([CH3:32])[CH3:31]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 176Acetic AcidHCID 36623923-((Tert-butyldimethylsilyl)oxy)propanalHCID 5049666Sodium triacetoxyborohydrideHCID 536301941-[2-(3-amino-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea

生成物 1

HCID 536301951-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea
収率 84%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 1-[2-(3-amino-phenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(pyridin-4-yloxy)-phenyl]-urea (100 mg, 0.23 mmol), 3-[(tert-butyldimethylsilyl)oxy]-1-propanal (47 mg, 0.25 mmol, 1.1 eq), and sodium triacetoxyborohydride (67 mg, 0.32 mmol, 1.4 eq) in anhydrous THF (2 mL) was added acetic acid (16 mg, 0.27 mmol, 1.2 eq). The reaction mixture was stirred under N2 at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 and extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4 and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 40:60 to 60:40 EtOAc/hexanes) to give 117 mg (84%) of 1-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea. 1H-NMR (DMSO-d6) δ 9.17 (s, 1H), 8.40 (dd, J=1.5 & 4.6 Hz, 2H), 8.31 (s, 1H), 7.48 (d, J=8.8 Hz, 2H), 7.17 (t, J=8.1 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.85 (dd, J=1.6 & 4.9 Hz, 2H), 6.61-6.56 (m, 3H), 6.32 (s, 1H), 5.92 (t, J=5.6 Hz, 1H), 3.66 (t, J=6.1 Hz, 2H), 3.07 (q, J=7.5 Hz, 2H), 1.72 (quintet, J=6.8 Hz, 2H), 1.26 (s, 9H), 0.84 (s, 9H), 0.02 (s, 6H); MS LC-MS [M+H]+=615.4, RT=3.28 min. Step 2: To a solution of 1-(5-tert-butyl-2-{3-[3-(tert-butyl-dimethyl-silanyloxy)-propylamino]-phenyl}-2H-pyrazol-3-yl)-3-[4-(pyridin-4-yloxy)-phenyl]-urea (117 mg, 0.19 mmol) in methanol (2 mL) was added a solution of 10% TFA in H2O (2 mL). The reaction was stirred at room temperature overnight. The mixture was then diluted with DCM, basified by the addition of saturated aq NaHCO3 and extracted with DCM. The combined organic phases were washed with brine, dried over MgSO4, and concentrated at reduced pressure. The crude residue was purified by MPLC (eluting with 4% to 5.5% MeOH in DCM) to give 82 mg (86%) of the desired product 1-{5-tert-butyl-2-[3-(3-hydroxy-propylamino)-phenyl]-2H-pyrazol-3-yl}-3-[4-(pyridin-4-yloxy)-phenyl]-urea. 1H-NMR (DMSO-d6) δ 9.18 (s, 1H), 8.40 (dd, J=1.7 & 4.7 Hz, 2H), 8.32 (s, 1H), 7.48 (d, J=9.0 Hz, 2H), 7.17 (t, J=7.9 Hz, 1H), 7.07 (d, J=9.1 Hz, 2H), 6.85 (dd, J=1.5 & 4.7 Hz, 2H), 6.63-6.56 (m, 3H), 6.33 (s, 1H), 5.91 (t, J=5.3 Hz, 1H), 4.47 (t, J=5.1 Hz, 1H), 3.48 (q, J=6.1 Hz, 2H), 3.06 (q, J=6.6 Hz, 2H), 1.69 (quintet, J=6.5 Hz, 2H), 1.26 (s, 9H); MS LC-MS [M+H]+=501.2, RT=2.29 min.

後処理

  1. customThe reaction mixture was quenched with saturated NaHCO3
  2. extractionextracted with EtOAc
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated at reduced pressure
  6. customThe crude residue was purified by MPLC (eluting with 40:60 to 60:40 EtOAc/hexanes)

出典と根拠

ORDレコード
ord-6c6ec60902974c91936a5e8c7603e3a3
出典データセット
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07838524B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート