Ethanolamine → 4-{2-[(2-Hydroxyethyl)amino]pyridin-4-yl}-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid

HRID 513196ノート

反応式

HRID 513196 の反応式
[K+].F[C:3]1[CH:8]=[C:7]([C:9]2[C:14]3[CH:15]=[C:16]([C:32]([O-:34])=[O:33])[N:17]([CH2:18][CH2:19][O:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=4)[C:13]=3[CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:5][N:4]=1.[CH2:35]([CH2:37][NH2:38])[OH:36]>N1C=CC=CC=1>[OH:36][CH2:35][CH2:37][NH:38][C:3]1[CH:8]=[C:7]([C:9]2[C:14]3[CH:15]=[C:16]([C:32]([OH:34])=[O:33])[N:17]([CH2:18][CH2:19][O:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:25][CH:26]=4)[C:13]=3[CH:12]=[CH:11][N:10]=2)[CH:6]=[CH:5][N:4]=1

参加物

4

反応物 2

HCID 700Ethanolamine2 回HCID 901862684-(2-Fluoropyridin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid potassium salt

生成物 1

HCID 712128074-{2-[(2-Hydroxyethyl)amino]pyridin-4-yl}-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid収率 63.7%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
120 °C

実験手順

4-(2-Fluoropyridin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid potassium salt (25 mg, 0.050 mmole) was taken up in pyridine (0.3 mL) in a screw cap vial. To this was added ethanolamine (0.015 mL, 0.250 mmole). The vial was capped then heated to 120° C. After stirring overnight ethanolamine (0.015 mL, 0.250 mmole) was added and heating continued. After stirring overnight the mixture was cooled to RT and concentrated. The crude material was taken up in DMSO and acidified with TFA. The resulting solution was purified by preparative reversed-phase HPLC (30×100 mm Phenomenex AXIA-Gemini-NX, 5%-95% CH3CN/water containing 0.1% TFA over 18 min at 50 mL/min) to give the title compound (16 mg, 52%) as a yellow solid. 1H NMR (499 MHz, DMSO): δ 8.58 (d, J=5.9 Hz, 1 H); 8.04 (d, J=6.7 Hz, 1 H); 7.95 (d, J=6.0 Hz, 1 H); 7.73 (s, 1 H); 7.66 (s, 1 H); 7.43 (d, J=6.6 Hz, 1 H); 7.23 (d, J=8.6 Hz, 2 H); 6.90 (d, J=8.8 Hz, 2 H); 5.13-5.04 (m, 2H); 4.39-4.35 (m, 2 H); 3.68 (m, 2 H); 3.49 (bs, 2 H). HRMS (ESI) calc (M+H)+=503.1537. found 503.1529.

後処理

  1. customcap vial
  2. customThe vial was capped
  3. additionwas added
  4. temperatureheating
  5. temperaturewas cooled to RT
  6. concentrationconcentrated
  7. customThe resulting solution was purified by preparative reversed-phase HPLC (30×100 mm Phenomenex AXIA-Gemini-NX, 5%-95% CH3CN/water containing 0.1% TFA over 18 min at 50 mL/min)

出典と根拠

ORDレコード
ord-73f94ee25d4e42ccab3cda536853a909
出典データセット
uspto-grants-2015_08
特許番号
US09102673B2

反応ノート

読み込み中…