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 513196Notes

Reaction equation

HRID 513196 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
120 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-73f94ee25d4e42ccab3cda536853a909
Source dataset
uspto-grants-2015_08
Patent number
US09102673B2

Reaction notes

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