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Nitrogen → 1-[7-[2-(1,3-dioxolan-2-yl)thiazol-4-yl]-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dione

HRID 1157773
Notes
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Reaction equation

HRID 1157773 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.[O:34]1[CH2:38][CH2:37][O:36][CH:35]1[C:39]1[S:40][CH:41]=[C:42]([Sn](C)(C)C)[N:43]=1.N#N>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>[O:34]1[CH2:38][CH2:37][O:36][CH:35]1[C:39]1[S:40][CH:41]=[C:42]([C:2]2[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]3[C:10]([C:11](=[O:31])[C:12]([N:14]4[CH2:19][CH2:18][N:17]([C:20]5[N:24]([C:25]6[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=6)[N:23]=[N:22][N:21]=5)[CH2:16][CH2:15]4)=[O:13])=[CH:9][NH:8][C:7]=23)[N:43]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 947NitrogenHCID 59511221HCID 59511221, compoundHCID 59511302HCID 59511302, compound

Product 1

HCID 497701741-[7-[2-(1,3-dioxolan-2-yl)thiazol-4-yl]-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dione

Reagents, catalysts & solvents 2

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a sealable 75 mL flask 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 (0.3 g, 0.643 mmol) was added a solution of 2-(1,3-dioxolan-2-yl)-4-(trimethylstannyl)thiazole (0.210 g, 0.655 mmol) in 1,4-Dioxane (10 ml). The mixture was flushed with N2 and Pd(PPh3)4 (0.149 g, 0.129 mmol) was added. The mixture was again flushed with N2, and the flask was sealed and heated in an oil bath to 100° C. After 20 h of heating, the mixture was cooled to rt. The mixture was transferred to a rb flask using MeOH as the transfer solvent. The solvent was removed under reduced pressure. The residue was re-dissolved in DMF, and was passed through a pad of celite to remove any remaining solids. The DMF solution was purified by prep HPLC. After the prep HPLC, a mostly-pure sample was collected as an off-white solid. A small portion of this material was removed and re-purified by flash chromatography (0-5% MeOH in dichloromethane gradient) [20 mg after the purification]. The remainder of the product was carried forward to the next step with no additional purification (0.305 g). LCMS: m/e 588.1 (M+H)+, ret time 1.30 min (method 3). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.20 (s, 1H) 8.38 (s, 1H) 8.22 (s, 1H) 8.11 (s, 1H) 7.68-7.72 (m, 2H) 7.57-7.66 (m, 3H) 6.29 (s, 1H) 4.16-4.20 (m, 2H) 4.07-4.10 (m, 2H) 3.99 (s, 3H) 3.67-3.71 (m, 2H) 3.41-3.45 (m, 2H) 3.30-3.32 (m, 2H) 3.15-3.19 (m, 2H).

Workup

  1. additionwas added
  2. customThe mixture was again flushed with N2
  3. customthe flask was sealed
  4. temperatureAfter 20 h of heating
  5. temperaturethe mixture was cooled to rt
  6. customThe mixture was transferred to a rb flask
  7. customThe solvent was removed under reduced pressure
  8. dissolutionThe residue was re-dissolved in DMF
  9. customto remove any remaining solids
  10. customThe DMF solution was purified by prep HPLC
  11. customAfter the prep HPLC, a mostly-pure sample was collected as an off-white solid
  12. customA small portion of this material was removed
  13. customre-purified by flash chromatography (0-5% MeOH in dichloromethane gradient) [20 mg
  14. customafter the purification]
  15. customThe remainder of the product was carried forward to the next step with no additional purification (0.305 g)
  16. customm/e 588.1 (M+H)+, ret time 1.30 min (method 3)

Sources & evidence

ORD record
ord-5f87bdca158f442f930cee1f0224d941
Source dataset
uspto-grants-2010_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07807676B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes