1-methyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazole → N-tert-butyl-2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246414Notes

Reaction equation

HRID 246414 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[CH3:26][N:27]1[C:35]2[CH2:34][CH2:33][CH2:32][CH2:31][C:30]=2[C:29]([Sn](CCCC)(CCCC)CCCC)=[N:28]1>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.[Cu]I>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:29]3[C:30]4[CH2:31][CH2:32][CH2:33][CH2:34][C:35]=4[N:27]([CH3:26])[N:28]=3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 2

HCID 712804701-methyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279752N-tert-butyl-2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 22.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 234 μmol) and 1-methyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazole (99.5 mg, 234 μmol) were dissolved in DMF (2.5 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (13.5 mg, 11.7 μmol) and CuI (8.91 mg, 46.8 μmol, Eq: 0.20) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 2.5 h. The reaction mixture was concentrated under high vacuum and the residue was purified by chromatography (60 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min) to give N-tert-butyl-2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (25 mg, 51.8 μmol, 22.1%) as an off-white solid. MS (M+Na)+=505; 1H NMR (CDCl3) δ: 9.12 (s, 1H), 8.33 (s, 1H), 8.02 (s, 1H), 5.73 (s, 2H), 3.90 (s, 3H), 3.54-3.68 (m, 2H), 3.06 (t, J=6.0 Hz, 2H), 2.63-2.78 (m, 2H), 1.91-2.06 (m, 2H), 1.77-1.90 (m, 2H), 1.62 (s, 9H), 0.95-1.02 (m, 2H), 0.00 (s, 9H).

Workup

  1. customthe mixture sonicated for 5 min with bubbling argon
  2. concentrationThe reaction mixture was concentrated under high vacuum
  3. customthe residue was purified by chromatography (60 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min)

Sources & evidence

ORD record
ord-f0fe02e0d885460aaa7f4d0dd3072c10
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…