Water → HCID 59511483, compound

HRID 1157779Notes

Reaction equation

HRID 1157779 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][N:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.C([N:36]([CH2:39][CH3:40])[CH2:37]C)C.[OH2:41].[CH:42]1(N)CC1>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>[CH:39]1([NH:36][C:37]([C:2]2[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]3[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]4[CH2:15][CH2:16][N:17]([C:20]5[N:24]([C:25]6[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=6)[N:23]=[N:22][N:21]=5)[CH2:18][CH2:19]4)=[CH:9][NH:8][C:7]=23)=[O:41])[CH2:40][CH2:42]1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 69828CyclopropylamineHCID 86620657HCID 86620657, compound

Product 1

HCID 59511483HCID 59511483, compoundYield 16.7%

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-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (0.076 g, 0.162 mmol) in Dioxane (4 mL) was added triethylamine (0.5 mL, 3.59 mmol), water (0.05 mL), cyclopropylamine (0.034 mL, 0.487 mmol), and tetrakis (0.038 g, 0.032 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 15 h, the mixture was cooled to 0° C. The excess CO was removed by vacuum, and the mixture was diluted with MeOH and was filtered through a pad of celite to remove the solids. The product was purified by prep HPLC to give N-cyclopropyl-4-methoxy-3-(2-oxo-2-(4-(1-(pyridin-2-yl)-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridine-7-carboxamide (0.014 g, 0.027 mmol, 16.7% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-D6) δ ppm 12.54 (s, 1H) 8.77 (s, 1H) 8.63-8.68 (m, 1H) 8.12-8.19 (m, 2H) 8.02 (s, 1H) 7.84 (d, J=7.93 Hz, 1H) 7.64 (dd, J=7.48, 4.73 Hz, 1H) 4.01 (s, 3H) 3.68-3.73 (m, 2H) 3.38-3.45 (m, 4H) 3.22-3.27 (m, 2H) 2.92-2.99 (m, 1H) 0.69-0.74 (m, 4H). LCMS: m/e 517.18 (M+H)+, ret time 1.378 min (method 3).

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. filtrationwas filtered through a pad of celite
  13. customto remove the solids
  14. customThe product was purified by prep HPLC

Sources & evidence

ORD record
ord-da4a018f7f6c4567be01c0214c197eb3
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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