Cesium carbonate → 3-(3-(1-Naphthyloxy)propyl)-1-(pyridin-3-ylmethyl)-7-(1,3,5-trimethyl-1h-pyrazol-4-yl)-1h-indole-2-carboxylic acid

HRID 576291Notes

Reaction equation

HRID 576291 reaction equation
[C:1]1([O:11][CH2:12][CH2:13][CH2:14][C:15]2[C:23]3[C:18](=[C:19]([C:24]4[C:25]([CH3:31])=[N:26][N:27]([CH3:30])[C:28]=4[CH3:29])[CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[C:32]([O:34]CC)=[O:33])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br.Br[CH2:39][C:40]1[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[C:1]1([O:11][CH2:12][CH2:13][CH2:14][C:15]2[C:23]3[C:18](=[C:19]([C:24]4[C:25]([CH3:31])=[N:26][N:27]([CH3:30])[C:28]=4[CH3:29])[CH:20]=[CH:21][CH:22]=3)[N:17]([CH2:39][C:40]3[CH:41]=[N:42][CH:43]=[CH:44][CH:45]=3)[C:16]=2[C:32]([OH:34])=[O:33])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 127070373-(Bromomethyl)pyridine hydrobromideHCID 68933185ethyl 3-(3-(naphthalen-1-yloxy)propyl)-7-(1,3,5-trimethyl-1H-pyrazol-4-yl)-1H-indole-2-carboxylate

Product 1

HCID 251446173-(3-(1-Naphthyloxy)propyl)-1-(pyridin-3-ylmethyl)-7-(1,3,5-trimethyl-1h-pyrazol-4-yl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of EXAMPLE 580A (90 mg), 3-(bromomethyl)pyridine hydrobromide (47.3 mg) and cesium carbonate (183 mg) in N,N-dimethylformamide (3.5 ml) was stirred at room temperature overnight. The insoluble material was filtered off and the filtrate was concentrated. The residue was suspended in tetrahydrofuran-methanol, and 10% NaOH was added. The resulting mixture was stirred at room temperature overnight and concentrated. The residue was dissolved in a mixture of DMSO and methanol. The solution was purified by reverse phase HPLC (mobile phase: 10%-100% acetonitrile in 0.1% TFA aqueous solution during 60 minutes) to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J=5.22 Hz, 1H), 8.23-8.28 (m, 1 H), 7.85-7.90 (m, 1 H), 7.80-7.85 (m, 2 H), 7.49-7.57 (m, 3 H), 7.45-7.49 (m, 1 H), 7.38-7.43 (m, 1 H), 7.19 (d, J=7.67 Hz, 1 H), 7.10-7.15 (m, 1 H), 6.92 (t, J=7.67 Hz, 2 H), 5.65 (d, J=17.49 Hz, 1 H), 5.44 (d, J=17.80 Hz, 1 H), 4.26 (t, J=5.98 Hz, 2 H), 3.62 (s, 3 H), 3.35-3.49 (m, 2 H), 2.24-2.32 (m, 2 H), 1.67 (s, 3 H), 1.59 (s, 3 H).

Workup

  1. filtrationThe insoluble material was filtered off
  2. concentrationthe filtrate was concentrated
  3. addition10% NaOH was added
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in a mixture of DMSO and methanol
  6. customThe solution was purified by reverse phase HPLC (mobile phase: 10%-100% acetonitrile in 0.1% TFA aqueous solution during 60 minutes)

Sources & evidence

ORD record
ord-45bf6e6639484f3383d52ec4cd89c4aa
Source dataset
uspto-grants-2015_05
Patent number
US09035047B2

Reaction notes

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