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 513196Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 513196
[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

Komponenten

4

Edukt 2

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

Produkt 1

HCID 712128074-{2-[(2-Hydroxyethyl)amino]pyridin-4-yl}-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acidAusbeute 63,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-73f94ee25d4e42ccab3cda536853a909
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102673B2

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