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Triphenylphosphine → 5-Cyclopropyl-N-methyl-2-(5-methylpyridin-2-yl)-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide

HRID 63541
ノート
印刷プレビュー

反応式

HRID 63541 の反応式
ClC1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:24]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:25][CH2:26]CC=C)[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=CC=1.[O:34]1[CH2:37][CH:36](CCO)[CH2:35]1.[C:41]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:46]=CC=C[CH:42]=1.CC(OC(/[N:66]=N/C(OC(C)C)=O)=O)C>C1COCC1.CCOC(C)=O>[CH:21]1([C:13]2[C:12]([N:24]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:25][CH2:26][CH:36]3[CH2:35][O:34][CH2:37]3)=[CH:11][C:10]3[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]4[CH:6]=[CH:7][C:41]([CH3:46])=[CH:42][N:66]=4)[N:9]=3)[CH:14]=2)[CH2:23][CH2:22]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 11776Triphenylphosphine2 回HCID 5363146Diisopropyl azodicarboxylate2 回HCID 108443452-(Oxetan-3-yl)ethan-1-olHCID 866990012-(4-Chlorophenyl)-5-cyclopropyl-N-methyl-6-[(methylsulfonyl)(pent-4-en-1-yl)amino]-2H-indazole-3-carboxamide

生成物 1

HCID 717666615-Cyclopropyl-N-methyl-2-(5-methylpyridin-2-yl)-6-{(methylsulfonyl)[2-(oxetan-3-yl)ethyl]amino}-2H-indazole-3-carboxamide
収率 59%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred suspension of 5-cyclopropyl-N-methyl-2-(5-methylpyridin-2-yl)-6-[(methylsulfonyl)amino]-2H-indazole-3-carboxamide (i) (11 mg, 0.03 mmol) and 2-(oxetan-3-yl)ethanol (5.6 mg, 0.06 mmol) in THF (200 μL) was added triphenylphosphine (11 mg, 0.04 mmol) followed by DIAD (8 μL, 0.04 mmol). The suspension dissolved slowly upon stirring. LCMS analysis of the reaction after 2.5 hr showed the presence of starting material and further aliquots of triphenylphosphine (5.0 mg, 0.05 mmol) and DIAD (8 μL, 0.04 mmol) were added. After stirring for 2 h, the reaction was diluted with EtOAc (10 mL), the organics washed with water (10 mL), brine (10 mL) and dried (MgSO4). The organics were concentrated in vacuo and the residue purified by automated column chromatography on silica gel (Biotage SP4, 4 g Grace Resolve cartridge) eluting with acetic acid: DCM (10% v/v, 10 CV) to remove the triphenylphosphine oxide followed by MeOH: DCM (gradient elution, 0% to 20%, 20 CV) to give Compound (5) (7.8 mg, 59%). ESI-MS m/z calculated for [M+H]+: 484.2. found: 484.2. 1H NMR (400 MHz, CDCl3) δ 8.47 (brs, 1H), 8.36 (s, 1H), 7.83-7.76 (m, 2H), 7.72 (s, 1H), 7.60 (s, 1H), 4.84-4.71 (m, 2H), 4.34 (q, J=6.0 Hz, 2H), 3.74-3.56 (m, 2H), 3.10-2.99 (m, 7H), 2.47 (s, 3H), 2.30 (ddd, J=13.6, 8.3, 5.4 Hz, 1H), 2.07-1.95 (m, 2H), 1.09-0.94 (m, 3H), 0.65-0.56 (m, 1H).

後処理

  1. dissolutionThe suspension dissolved slowly
  2. customLCMS analysis of the reaction after 2.5 hr
  3. additionwere added
  4. stirringAfter stirring for 2 h
  5. washthe organics washed with water (10 mL), brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationThe organics were concentrated in vacuo
  8. customthe residue purified by automated column chromatography on silica gel (Biotage SP4, 4 g Grace Resolve cartridge)
  9. washeluting with acetic acid
  10. customDCM (10% v/v, 10 CV) to remove the triphenylphosphine oxide

出典と根拠

ORDレコード
ord-6383373a85ef46b2ac94a48bb421955e
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09447080B2

反応ノート

読み込み中…

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