Acetic Acid → N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide

HRID 1669088Notes

Reaction equation

HRID 1669088 reaction equation
N1CC[O:4]CC1.C[CH:8]1[CH2:25][C:24]2[C:10](=[CH:11][C:12]3[N+:17]([O-:18])=NC(CCC=O)=[N:14][C:13]=3[CH:23]=2)[CH2:9]1.[BH3-]C#N.[Na+].[CH3:30][C:31]([OH:33])=O>CCO>[N+:17]([C:12]1[CH:11]=[C:10]2[C:24]([CH2:25][CH2:8][CH2:9]2)=[CH:23][C:13]=1[NH:14][C:31](=[O:33])[CH3:30])([O-:18])=[O:4]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 119521843-(7-Methyl-1-oxido-7,8-dihydro-6h-indeno[5,6-e][1,2,4]triazin-3-yl)propanal

Product 1

HCID 10751392N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Morpholine (0.64 mL, 7.3 mmol) was added to a solution of aldehyde 101 (0.47 g, 1.8 mmol) in EtOH (20 mL) at 0° C. and the solution stirred for 30 min. NaCNBH3 (0.35 g, 5.5 mmol) was added and the mixture stirred at 0° C. for 30 min, then HOAc (0.5 mL) was added and the mixture stirred at 20° C. for 30 min. The solvent was evaporated and the residue partitioned between DCM and water, the organic phase was dried, the solvent evaporated and the residue purified by chromatography, eluting with a gradient (0-10%) of MeOH/EtOAc, to give (i) starting material 101 (83 mg, 17%) and (ii) alcohol 103 (134 mg, 28%) as a white solid: mp (MeOH/EtOAc) 70-71° C.; 1H NMR δ 8.21 (s, 1H, H-9), 7.71 (s, 1H, H-5), 3.78 (t, J=6.1 Hz, 2H, CH2O), 3.20-3.28 (m, 2H, CH2), 3.15 (t, J=7.2 Hz, 2H, CH2), 2.64-2.78 (m, 3H, H-7, CH2), 2.35 (br s, 1H, OH), 2.12-2.19 (m, 2H, CH2), 1.19 (d, J=6.4 Hz, 3H, CH3); 13C NMR δ 165.7, 154.6, 148.7, 147.3, 132.3, 122.6, 114.4, 62.1, 41.2, 40.9, 35.0, 30.6, 24.7, 20.2. Anal. calcd for C14H17N3O2.¼H2O: C, 63.7; H, 6.7; N, 15.9. Found: C, 63.7; H, 6.6; N, 15.9%; and (iii) 1-oxide 102 (331 mg, 55%) as a yellow gum: 1H NMR δ 8.22 (s, 1H, H-9), 7.70 (s, 1H, H-5), 3.60 (br t, J=4.7 Hz, 4H, 2×CH2O), 3.21-3.28 (m, 2H, CH2), 3.05 (br t, J=7.4 Hz, 2H, CH2), 2.65-2.77 (m, 3H, H-7, CH2), 2.47-2.54 (m, 6H, 3×CH2N), 2.11 (p, J=7.3 Hz, 2H, CH2), 1.19 (d, J=6.4 Hz, 3H, CH3); 13C NMR δ 165.7, 154.4, 148.5, 147.5, 132.3, 122.7, 114.4, 66.7 (2), 55.1, 53.5 (2), 41.2, 40.9, 35.2, 35.0, 24.7, 20.2; MS (FAB+) m/z 392 (MH+, 100%), 311 (20); HRMS (FAB+) calcd for C18H25N4O2 (MH+) m/z 329.1978, found 329.1978.

Workup

  1. stirringthe mixture stirred at 0° C. for 30 min
  2. stirringthe mixture stirred at 20° C. for 30 min
  3. customThe solvent was evaporated
  4. customthe residue partitioned between DCM and water
  5. customthe organic phase was dried
  6. customthe solvent evaporated
  7. customthe residue purified by chromatography
  8. washeluting with a gradient (0-10%) of MeOH/EtOAc

Sources & evidence

ORD record
ord-92affa9d25d04894b92bee5b3cc88ec2
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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