(3-(tributylstannyl)-1H-pyrazol-5-yl)methanol → 1-[7-[5-(hydroxymethyl)-1H-pyrazol-3-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 1157760Notes

Reaction equation

HRID 1157760 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.C([Sn](CCCC)(CCCC)[C:39]1[CH:43]=[C:42]([CH2:44][OH:45])[NH:41][N:40]=1)CCC>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:45][CH2:44][C:42]1[NH:41][N:40]=[C:39]([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)[CH:43]=1

Participants

5

Reactant 2

HCID 59511207(3-(tributylstannyl)-1H-pyrazol-5-yl)methanolHCID 59511221HCID 59511221, compound

Product 1

HCID 248747561-[7-[5-(hydroxymethyl)-1H-pyrazol-3-yl]-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dioneYield 21.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a sealable, flask a mixture of 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 (0.150 g, 0.321 mmol) in 1,4-dioxane (5 mL) was prepared. (3-(tributylstannyl)-1H-pyrazol-5-yl)methanol (0.137 g, 0.353 mmol) was added followed by tetrakis(triphenylphosphine)palladium (0) (0.150 g, 0.130 mmol). The mixture was flushed with N2, and flask was sealed. The mixture was then heated to 120° C. for 14 h. After cooling to rt, the mixture was diluted with DMF, and filtered through a plug of celite to remove any solids. The liquid was concentrated under reduced pressure, and the residue was dissolved in DMF. The DMF solution was purified by prep HPLC to give 0.037 g of an off-white solid as the 1-(7-(5-(hydroxymethyl)-1H-pyrazol-3-yl)-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. LCMS: m/e 529.2 (M+H)+, ret time 1.78 min (method 2). 1H NMR (500 MHz, MeOD) δ ppm 8.65 (s, 1H) 7.98 (s, 1H) 7.56-7.80 (m, 5H) 7.16 (s, 1H) 4.81 (s, 2H) 4.15 (s, 3H) 3.83-3.87 (m, 2H) 3.63-3.68 (m, 2H) 3.40-3.44 (m, 2H) 3.34-3.39 (m, 2H).

Workup

  1. customwas prepared
  2. customThe mixture was flushed with N2, and flask
  3. customwas sealed
  4. temperatureAfter cooling to rt
  5. additionthe mixture was diluted with DMF
  6. filtrationfiltered through a plug of celite
  7. customto remove any solids
  8. concentrationThe liquid was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in DMF
  10. customThe DMF solution was purified by prep HPLC

Sources & evidence

ORD record
ord-740bc63875f24ac79cbbfb8ca0ce72a8
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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