Methanol → 4-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indole

HRID 751312Notes

Reaction equation

HRID 751312 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[C:23]2[C:18](=[C:19]([C:24]3[C:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)=[N:27][N:26]4[CH2:35][CH2:36][CH2:37][C:25]=34)[CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16]1)=O)(C)(C)C.CO.[OH-].[NH4+]>C(Cl)Cl>[N:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C:28]1[C:24]([C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:18]=2[CH:17]=[CH:16][NH:15]3)=[C:25]2[CH2:37][CH2:36][CH2:35][N:26]2[N:27]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 586119614-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-indole-1-carboxylic Acid tert-Butyl Ester

Product 1

HCID 103800614-[2-(Pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-1H-indoleYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Add trifluoroacetic acid (0.4 mL) to a solution of 4-[2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-indole-1-carboxylic acid tert-butyl ester (34 mg, 0.085 mmol) in methylene chloride (2 mL) at 0° C. Allow the reaction to warm to room temperature slowly over 19 h. Dilute the reaction with methylene chloride and methanol. Add concentrated aqueous ammonium hydroxide (2 mL) and concentrate in vacuo. Purify by flash column chromatography, using the appropriate mixture of methylene chloride, chloroform, methanol, and concentrated aqueous ammonium hydroxide, to provide 11 mg (8% yield over 2 steps) of the title compound as a white solid. MS (APCI) m/e 301 (M+1). 1H NMR (DMSO-d6) δ 10.98 (s, 1H), 8.30 (d, J=4 Hz, 1H), 7.65 (td, J=8, 2 Hz, 1H), 7.46 (d, J=8 Hz, H), 7.26 (d, J=8 Hz, 1H), 7.17-7.13 (m, 2H), 7.00 (t, J=8 Hz, 1H), 6.81 (d, J=7 Hz, 1H), 4.21 (t, J=7 Hz, 2H), 2.85 (dd, J=8, 7 Hz, 2H), 2.64-2.55 (m, 2H). HPLC: >99%, Rt=15.1 min. TLC (SiO2): Rf0.2 (1:1 methylene chloride/[80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]).

Workup

  1. customthe reaction
  2. additionDilute
  3. concentrationconcentrate in vacuo
  4. customPurify by flash column chromatography
  5. additionthe appropriate mixture of methylene chloride, chloroform, methanol, and concentrated aqueous ammonium hydroxide

Sources & evidence

ORD record
ord-bffa4c4824d64706b927103871ba57b5
Source dataset
uspto-grants-2008_07
Patent number
US07405299B2

Reaction notes

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