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Triphenylphosphine → 1-(5-tert-Butyl-2-{3-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea Formate Salt

HRID 572095
ノート
印刷プレビュー

反応式

HRID 572095 の反応式
CC([O:4][C:5](/N=N/C(OC(C)C)=O)=[O:6])C.[C:15]([C:19]1[CH:20]=[C:21]([NH:31][C:32]([NH:34][C@@H:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C@H:38]([O:45][C:46]3[CH:47]=[CH:48][C:49]4[N:50]([C:52]([CH:55]([CH3:57])[CH3:56])=[N:53][N:54]=4)[CH:51]=3)[CH2:37][CH2:36]2)=[O:33])[N:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)[N:23]=1)([CH3:18])([CH3:17])[CH3:16].[OH:58][CH:59]1[CH2:64][CH2:63][N:62]([CH2:65][CH2:66]O)[CH2:61][CH2:60]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH:5]([OH:6])=[O:4].[C:15]([C:19]1[CH:20]=[C:21]([NH:31][C:32]([NH:34][C@@H:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[C@H:38]([O:45][C:46]3[CH:47]=[CH:48][C:49]4[N:50]([C:52]([CH:55]([CH3:57])[CH3:56])=[N:53][N:54]=4)[CH:51]=3)[CH2:37][CH2:36]2)=[O:33])[N:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH2:66][CH2:65][N:62]3[CH2:63][CH2:64][CH:59]([OH:58])[CH2:60][CH2:61]3)[CH:25]=2)[N:23]=1)([CH3:18])([CH3:17])[CH3:16]
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 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 147994684-Hydroxy-1-piperidineethanolHCID 866867021-[5-tert-Butyl-2-(3-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

生成物 1

HCID 86686704
1-(5-tert-Butyl-2-{3-[2-(4-hydroxy-piperidin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea Formate Salt

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

DIAD (51.0 μL, 0.260 mmol) was added to a solution of Intermediate 22d (75.0 mg, 0.13 mmol), 4-hydroxy-1-piperidine-ethanol (28.0 mg, 0.19 mmol), and Ph3P (68.0 mg, 0.26 mmol) in THF (1.5 mL) at 0° C. The reaction was stirred at RT over the weekend then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM. Further purification by HPLC (C18 X-select column, 25-98% MeCN in H2O, 0.1% HCO2H) gave the title compound as a white powder after freeze-drying (57 mg, 62%). LCMS (Method 5): Rt 3.32 min, m/z 707.4 [MH+]. 1H NMR (400 MHz, d4-MeOD): 1.31 (9H, s), 1.42 (3H, d, J 6.8), 1.45 (3H, d, J 6.8), 1.62-1.72 (2H, m), 1.86-2.04 (4H, m), 2.04-2.14 (1H, m), 2.21-2.30 (1H, m), 2.69-2.79 (2H, m), 3.11-3.19 (4H, m), 3.51 (1H, sept, J 6.9), 3.70-3.78 (1H, m), 4.26 (2H, t, J 5.3), 4.89 (1H, dd, J 8.9, 5.8), 5.45 (1H, t, J 4.1), 6.33 (1H, s), 7.05 (1H, ddd, J 8.4, 2.7, 0.8), 7.09-7.13 (2H, m), 7.19-7.25 (3H, m), 7.26-7.33 (2H, m), 7.42 (1H, t, J 8.1), 7.61 (1H, dd, J 9.7, 0.6), 8.01 (1H, d, J 1.7), 8.42 (1H, br s).

後処理

  1. customthen partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by FCC
  8. customFurther purification by HPLC (C18 X-select column, 25-98% MeCN in H2O, 0.1% HCO2H)

出典と根拠

ORDレコード
ord-f4ccf0332a0741b9ad6318c74067287d
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09029373B2

反応ノート

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