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Potassium Phosphate, Tribasic → 5-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine

HRID 634134
ノート
印刷プレビュー

反応式

HRID 634134 の反応式
[N:1]1([C:6]2[CH:11]=[CH:10][CH:9]=[C:8](B3OC(C)(C)C(C)(C)O3)[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.I[C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:31]3[S:35][C:34]([NH2:36])=[N:33][N:32]=3)[CH:29]=2)[N:24](S(C2C=CC(C)=CC=2)(=O)=O)[CH:23]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O>[N:1]1([C:6]2[N:7]=[C:8]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]5[S:35][C:34]([NH2:36])=[N:33][N:32]=5)[CH:29]=4)[NH:24][CH:23]=3)[CH:9]=[CH:10][CH:11]=2)[CH2:2][CH2:3][CH2:4][CH2:5]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

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)HCID 457857172-(Pyrrolidin-1-YL)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridineHCID 68328527HCID 68328527、化合物

生成物 1

HCID 683283905-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine収率 8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 3776Isopropanol溶媒

反応条件

温度
100 °C

実験手順

A glass microwave reaction vessel was charged with 2-(pyrrolidin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (46 mg, 0.17 mmol, CombiPhos Catalysts, Inc.) and 5-(3-iodo-1-tosyl-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (060 g, 0.12 mmol) in 66% IPA in H2O (1 mL) followed by Amphos (4 mg, 6 μmol), potassium phosphate (0.077 g, 0.36 mmol). The mixture was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 10 min. The aqueous layer was removed and the resulting mixture was concentrated in vacuo and purified by preparative HPLC. The product was dissolved in p-dioxane (1 mL) and aq. NaOH (1 M, 0.1 mL) was added. The solution was heated in a microwave at 100° C. for 10 min, and purified by preparative HPLC to give 5-(3-(6-(1-pyrrolidinyl)-2-pyridinyl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-amine (3 mg, 8%). MS (ESI, pos. ion) m/z: 364 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 8.23 (1H, s), 8.00 (1H, s), 7.91 (1H, dd, J=9.0, 7.6 Hz), 7.65 (1H, d, J=8.6 Hz), 7.58 (1H, d, J=8.6 Hz), 7.09 (1H, d, J=7.2 Hz), 6.85 (1H, d, J=9.0 Hz), 3.60-3.68 (4H, m), 2.06-2.14 (4H, m).

後処理

  1. customA glass microwave reaction vessel
  2. customThe aqueous layer was removed
  3. concentrationthe resulting mixture was concentrated in vacuo
  4. custompurified by preparative HPLC
  5. dissolutionThe product was dissolved in p-dioxane (1 mL)
  6. additionaq. NaOH (1 M, 0.1 mL) was added
  7. temperatureThe solution was heated in a microwave at 100° C. for 10 min
  8. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-e8894fc6ebd64df8b9a8a227b5fc2fdf
出典データセット
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09321756B2

反応ノート

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