Tetrahydrofuran → 6-Bromo-1-(cyclopropylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205949Notes

Reaction equation

HRID 2205949 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[NH:10][C:4]=2[CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[CH2:27]1[CH2:31]O[CH2:29][CH2:28]1.BrCC1CC1>CN(C=O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[Br:1][C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[N:10]([CH2:29][CH:28]3[CH2:31][CH2:27]3)[C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 81503BromomethylcyclopropaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 867062766-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine

Product 1

HCID 867063096-Bromo-1-(cyclopropylmethyl)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridineYield 82.2%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

6-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine (Preparation 22, 100 mg, 0.36 mmole) was azeotroped with toluene (3 mL) and dissolved in DMF (1 mL). To the solution was added sodium hexamethyldisilazide, 1M in THF (0.4 mL, 0.4 mmole) and the reaction was stirred at room temperature for 20 minutes. Bromomethylcyclopropane (78 uL, 108 mg, 0.8 mmole) was added and the reaction was stirred at room temperature for 6 hours. Ethyl acetate (25 mL) was added and the solution was washed with water (3×10 mL) and with brine (5 mL), dried and evaporated in vacuo. The crude product was purified using preparative TLC eluting with ethyl acetate to afford the title compound (98 mg, 82%). 1H-NMR (CDCl3, 500 MHz): δ 0.23 (m, 2H), 0.55 (m, 2H), 1.12 (m, 1H), 4.03 (s, 3H), 4.07 (d, J=6.31 Hz, 2H), 6.54 (d, J=0.95 Hz, 1H), 7.45 (t, J=0.95 Hz, 1H), 7.61 (s, 1H), 7.71 (d, J=0.95 Hz, 1H), 8.61 (d, J=0.95 Hz, 1H).

Workup

  1. stirringthe reaction was stirred at room temperature for 6 hours
  2. washthe solution was washed with water (3×10 mL) and with brine (5 mL)
  3. customdried
  4. customevaporated in vacuo
  5. customThe crude product was purified
  6. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-8d3b6413f7c04148899e9fd828930265
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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