Sodium Hydroxide → HCID 20780127, compound

HRID 1295852Notes

Reaction equation

HRID 1295852 reaction equation
C[Al](C)C.[CH:5]1([CH2:8][NH:9][CH2:10][CH2:11][CH3:12])[CH2:7][CH2:6]1.C(O[C:16]([C:18]1[N:22]2[C:23]3[CH:24]=[C:25]([F:39])[CH:26]=[CH:27][C:28]=3[N:29]([C:30]3[C:35]([CH3:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=3[CH3:38])[C:21]2=[N:20][C:19]=1[CH3:40])=[O:17])C.[OH-].[Na+]>C1C=CC=CC=1>[CH:5]1([CH2:8][N:9]([CH2:10][CH2:11][CH3:12])[C:16]([C:18]2[N:22]3[C:23]4[CH:24]=[C:25]([F:39])[CH:26]=[CH:27][C:28]=4[N:29]([C:30]4[C:35]([CH3:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=4[CH3:38])[C:21]3=[N:20][C:19]=2[CH3:40])=[O:17])[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 117787Cyclopropanemethanamine, N-propyl-HCID 16682925TrimethylaluminumHCID 20780190HCID 20780190, compound

Product 1

HCID 20780127HCID 20780127, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

A solution of trimethylaluminum (2.0 M in heptane, 1.4 mL, 2.8 mmol) was added to a solution of N-cyclopropylmethyl-N-propylamine (0.40 mL, 2.8 mmol) in benzene (3 mL) at 0° C. The mixture was warmed up to room temperature and stirred at this temperature for 1.5 hours, and then added to a stirred solution of 5-fluoro-2-methyl-8-(2,4,6-trimethyl-phenyl)-8H-1,3a,8-triaza-cyclopenta[a]indene-3-carboxylic acid ethyl ester (0.13 g, 0.35 mmol) in benzene (2.0 mL). The mixture was refluxed for 12 hours. Upon cooling at 0° C., 1 N sodium hydroxide (15 mL) was added dropwise to the above mixture. The mixture was extracted with dicholoromethane (30 mL), and the organic layer was dried over anhydrous sodium sulfate. Solvents were removed in vacuo and the residue was subjected to chromatography using ethyl acetate/hexanes (3:7) as eluent to afford the title compound as an off-white solid (0.156 g, 100% yield). 1H NMR (CDCl3, 300 MHz) δ 7.60 (dd, J=8.7, 2.5 Hz, 1H), 6.99 (s, 2H), 6.92 (td, J=9.0, 2.5 Hz, 1H), 6.75 (dd, J=8.8, 4.4 Hz, 1H), 3.66 (t, J=7.1 Hz, 2H), 3.46 (d, J=6.9 Hz, 2H), 2.35 (s, 3H), 2.32 (s, 3H), 1.92 (s, 6H), 1.71-1.63 (m, 2H), 1.11-1.05 (m, 1H), 0.88 (t, J=7.2 Hz, 3H), 0.57-0.53 (m, 2H), 0.19-0.16 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 163.6, 159.4, 156.3, 148.9, 143.3, 139.4, 137.0, 131.6, 129.7, 128.7, 124.8 (d, J=13 Hz), 114.2, 110.6 (d, J=25 Hz), 101.2 (d, J=29 Hz), 51.3, 48.6, 21.1, 21.0, 17.8, 15.7, 11.3, 10.1, 3.8. LC/MS: tR=1.95 min, 447.22 (MH+).

Workup

  1. temperatureThe mixture was refluxed for 12 hours
  2. temperatureUpon cooling at 0° C.
  3. extractionThe mixture was extracted with dicholoromethane (30 mL)
  4. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  5. customSolvents were removed in vacuo

Sources & evidence

ORD record
ord-2f8585b83b7c4b359379429097e31dab
Source dataset
uspto-grants-2007_07
Patent number
US07244746B2

Reaction notes

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