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Sodium Hydroxide → 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine

HRID 634254
ノート
印刷プレビュー

反応式

HRID 634254 の反応式
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:24][N:23]=[C:22]([NH:25]CC5C=CC(OC)=CC=5)[N:21]=4)[CH:18]=3)[N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C(OC1N=C(C2C3C(=CC=C(C4SN=C(N)N=4)C=3)N(S(C3C=CC(C)=CC=3)(=O)=O)C=2)C=CC=1)(C)C.[OH-].[Na+]>C(O)(C(F)(F)F)=O.O1CCOCC1>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:20]4[S:24][N:23]=[C:22]([NH2:25])[N:21]=4)[CH:18]=3)[NH:13][CH:12]=2)[CH:8]=[CH:7][CH:6]=1)([CH3:3])[CH3:2]
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 3

HCID 14798Sodium HydroxideHCID 683283525-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amineHCID 683284615-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine

生成物 1

HCID 683281695-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine収率 17.5%

試薬・触媒・溶媒 2

HCID 6422
Trifluoroacetic acid
溶媒
HCID 312751,4-Dioxane溶媒

実験手順

A solution of 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.35 g, 0.56 mmol) in TFA (3.5 mL) was heated in a Biotage microwave at 100° C. for 30 min. The reaction was cooled to RT. TFA was removed in vacuo and the residue was washed with Et2O (7 mL) to get the crude product (250 mg), which was used in next step without further purification. MS (ESI, pos. ion) m/z: 506.1 (M+1). To a solution of crude 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (0.25 g, 0.442 mmol) in 1,4-dioxane (2.5 mL) was added 10% aq NaOH (1.3 mL) and the reaction was heated at 100° C. for 2 h. The mixture was treated with ice cold water (10 mL), resulting a white precipitate. The precipitate was filtered and washed with ice cold water (˜10 mL) and dried under vacuum. The solid was purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in H2O with 0.01% TFA) to give 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-thiadiazol-3-amine (30 mg, 17.5%). MS (ESI, pos. ion) m/z: 352.1 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 11.96 (s, 1H), 9.05 (d, J=1.2 Hz, 1H), 8.25 (d, J=2.8 Hz, 1H), 7.76 (dd, J=8.4, 1.6 Hz, 1H), 7.69-7.65 (m, 2H), 7.64 (d, J=8.4 Hz, 1H), 7.46 (t, J=7.2 Hz, 2H), 6.70 (s, 2H), 6.54 (d, J=8 Hz, 1H), 5.61-5.55 (m, 1H), 1.52 (d, J=5.6 Hz, 6H).

後処理

  1. customTFA was removed in vacuo
  2. washthe residue was washed with Et2O (7 mL)
  3. customto get the crude product (250 mg), which
  4. customwas used in next step without further purification
  5. temperaturethe reaction was heated at 100° C. for 2 h
  6. customresulting a white precipitate
  7. filtrationThe precipitate was filtered
  8. washwashed with ice cold water (˜10 mL)
  9. customdried under vacuum
  10. customThe solid was purified by preparative HPLC (eluent: 10-70% MeCN:MeOH (1:1) in H2O with 0.01% TFA)

出典と根拠

ORDレコード
ord-ab3a4cf564aa4b9a8c6b0ea4206ade4f
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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