Ethanolamine → HCID 59511466, compound

HRID 1157778Notes

Reaction equation

HRID 1157778 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.[CH2:34]([N:36]([CH2:39]C)CC)[CH3:35].[OH2:41].C(CN)[OH:43]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:41][CH2:35][CH2:34][NH:36][C:39]([C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]3[CH2:15][CH2:16][N:17]([C:20]4[N:24]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:23]=[N:22][N:21]=4)[CH2:18][CH2:19]3)=[CH:9][NH:8][C:7]=12)=[O:43]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 962WaterHCID 8471TriethylamineHCID 59511221HCID 59511221, compound

Product 1

HCID 59511466HCID 59511466, compoundYield 41.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stainless steel pressure vessel containing 1-(7-chloro-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (0.16 g, 0.343 mmol) in Dioxane (10 mL) was added triethylamine (0.7 mL, 5.02 mmol), water (0.05 mL), ethanolamine (0.021 mL, 0.343 mmol), and tetrakis (0.079 g, 0.069 mmol). The mixture was flushed with N2. The stainless steel pressure vessel was purged of air, and refilled with N2 three times. After the final fill with N2, the N2 was removed by vacuum. The vessel was filled and purged with 50 psi carbon monoxide three times, then filled the vessel to an initial reaction pressure of 90 psi of carbon monoxide. The vessel was heated in an oil bath at 100° C. After 16 h, the mixture was cooled to 0° C. The excess CO was removed by vacuum, and the mixture was diluted with MeOH and was transferred to a flask. The mixture was concentrated under reduced pressure. The residue was taken up in DMF, and was filtered through a pad of celite to remove any solids. The DMF solution was purified by prep HPLC. After the first purification, the product was purified a second time using a biotage 25+M cartridge and a 0-5% MeOH in dichloromethane as the gradient. The product, N-(2-hydroxyethyl)-4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridine-7-carboxamide (0.074 g, 0.142 mmol, 41.6% yield), was isolated as a white solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 12.53 (s, 1H) 8.66 (s, 1H) 8.12 (s, 1H) 8.07 (s, 1H) 7.56-7.72 (m, 5H) 4.83 (t, J=5.49 Hz, 1H) 4.02 (s, 3H) 3.66-3.70 (m, 2H) 3.57 (q, J=5.90 Hz, 2H) 3.39-3.46 (m, 4H) 3.28-3.32 (m, 2H) 3.17 (d, J=3.36 Hz, 2H). LCMS: m/e 520.32 (M+H)+, ret time 2.165 min (method 4).

Workup

  1. customThe mixture was flushed with N2
  2. customThe stainless steel pressure vessel was purged of air
  3. additionrefilled with N2 three times
  4. customAfter the final fill with N2, the N2 was removed by vacuum
  5. additionThe vessel was filled
  6. custompurged with 50 psi carbon monoxide three times
  7. additionfilled the vessel to an initial
  8. customreaction pressure of 90 psi of carbon monoxide
  9. temperaturethe mixture was cooled to 0° C
  10. customThe excess CO was removed by vacuum
  11. additionthe mixture was diluted with MeOH
  12. customwas transferred to a flask
  13. concentrationThe mixture was concentrated under reduced pressure
  14. filtrationwas filtered through a pad of celite
  15. customto remove any solids
  16. customThe DMF solution was purified by prep HPLC
  17. customAfter the first purification
  18. customthe product was purified a second time

Sources & evidence

ORD record
ord-beba99f0fe604421b6e959495a455ced
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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