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Potassium Phosphate, Tribasic → 5-cyclopropyl-2-(4-cyclopropylphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide

HRID 1037543
ノート
印刷プレビュー

反応式

HRID 1037543 の反応式
Br[C:2]1[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]([CH2:29][CH2:30][CH2:31][OH:32])[S:25]([CH3:28])(=[O:27])=[O:26])[C:13]([CH:21]4[CH2:23][CH2:22]4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.[CH:33]1(B(O)O)[CH2:35][CH2:34]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:21]1([C:13]2[C:12]([N:24]([CH2:29][CH2:30][CH2:31][OH:32])[S:25]([CH3:28])(=[O:26])=[O:27])=[CH:11][C:10]3[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]4[CH:4]=[CH:3][C:2]([CH:33]5[CH2:35][CH2:34]5)=[CH:7][CH:6]=4)[N:9]=3)[CH:14]=2)[CH2:23][CH2:22]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 569627692-(4-bromophenyl)-5-cyclopropyl-6-[3-hydroxypropyl(methylsulfonyl)amino]-N-methyl-indazole-3-carboxamide

生成物 1

HCID 675128685-cyclopropyl-2-(4-cyclopropylphenyl)-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide
収率 27.3%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

To a degassed mixture of 2-(4-bromophenyl)-5-cyclopropyl-6-[(3-hydroxypropyl)(methylsulfonyl)amino]-N-methyl-2H-indazole-3-carboxamide (10 mg, 0.019 mmol), cyclopropylboronic acid (5 mg, 0.058 mmol), potassium phosphate (17 mg, 0.080 mmol) in toluene (0.5 mL) and water (50 μL) were added tricyclohexylphosphine (1 mg, 0.0038 mmol) and Pd(OAc)2 (0.4 mg, 0.0019 mmol) and the reaction was heated at 100° C. for 2 h. The mixture was concentrated to dryness and purified by preparative LCMS (5-40-100% ACN in 0.1 aqueous formic acid) to afford Compound (53) as a white solid (2.5 mg, 27%). ESI-MS m/z calculated for [M+H]+: 483.2; found: 483.2; 1H NMR (400 MHz, MeOD) δ 7.85 (s, 1H), 7.58-7.43 (m, 2H), 7.39 (s, 1H), 7.28 (d, J=8.5 Hz, 2H), 4.06-3.81 (m, 2H), 3.76-3.57 (m, 2H), 3.17 (s, 3H), 2.94 (s, 3H), 2.54-2.34 (m, 1H), 2.19-1.96 (m, 1H), 1.96-1.68 (m, 2H), 1.21-0.94 (m, 5H), 0.85-0.76 (m, 2H), 0.75-0.59 (m, 1H).

後処理

  1. concentrationThe mixture was concentrated to dryness
  2. custompurified by preparative LCMS (5-40-100% ACN in 0.1 aqueous formic acid)

出典と根拠

ORDレコード
ord-6fc317b78fec4584bcec91c906a7a3b8
出典データセット
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08546389B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート