Hexabutyldistannane → methyl2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate

HRID 246773Notes

Reaction equation

HRID 246773 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:9]=2)[N:4]([CH3:15])[N:3]=1.Br[C:17]1[N:22]=[C:21]2[C:23]([C:34]([O:36][CH3:37])=[O:35])=[CH:24][N:25]([CH2:26][O:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[C:20]2=[N:19][CH:18]=1.CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC>CN(C=O)C.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>[CH3:37][O:36][C:34]([C:23]1[C:21]2=[N:22][C:17]([C:2]3[C:10]4[C:5](=[CH:6][CH:7]=[C:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:9]=4)[N:4]([CH3:15])[N:3]=3)=[CH:18][N:19]=[C:20]2[N:25]([CH2:26][O:27][C:28](=[O:33])[C:29]([CH3:31])([CH3:30])[CH3:32])[CH:24]=1)=[O:35]

Participants

6

Reactant 3

HCID 6327815HexabutyldistannaneHCID 712795273-iodo-1-methyl-5-(methylsulfonyl)-1H-indazoleHCID 86677991methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

Product 1

HCID 71280530methyl2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylateYield 70.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-iodo-1-methyl-5-(methylsulfonyl)-1H-indazole (127 mg, 0.37 mmol), methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (128 mg, 0.34 mmol) and Pd(PPh3)4 (20 mg, 0.017 mmol) in DMF (8 mL) was added hexa-N-butylditin (299 mg, 0.51 mmol). The reaction mixture was degassed by bubbling nitrogen for 3 minutes and refilled with nitrogen. The mixture was heated to 100° C. for 15 hours under nitrogen. After cooling to room temperature, water (40 mL) was added and product extracted with EtOAc (3×30 mL), organics combined dried with sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with EtOAc/petroleum ether=2:1) to give methyl2-(1-methyl-5-(methylsulfonyl)-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (120 mg, 69.7%) as an off-white solid. LCMS: (M+H)+=500; 1H NMR (300 MHz, DMSO): δ 9.43 (d, 1H, J=1.2 Hz), 9.21 (s, 1H), 8.95 (d, 1H, J=1.2 Hz), 8.77 (s, 1H), 8.01 (s, 1H), 6.33 (s, 2H), 4.24 (s, 3H), 4.04 (s, 3H), 3.28 (s, 3H), 1.09 (s, 9H).

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen for 3 minutes
  3. additionrefilled with nitrogen
  4. temperatureAfter cooling to room temperature
  5. additionwater (40 mL) was added
  6. extractionproduct extracted with EtOAc (3×30 mL)
  7. dry with materialorganics combined dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with EtOAc/petroleum ether=2:1)

Sources & evidence

ORD record
ord-65ca3814bb25461bb5f86b9451f1696d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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