Ethyl orthoformate → HCID 57618481, compound

HRID 1690708Notes

Reaction equation

HRID 1690708 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[C:15]4[CH2:27][C:26]5[C:21](=[CH:22][CH:23]=[C:24]([NH2:28])[CH:25]=5)[C:16]=4[NH:17][C:18]=3[C:19]=2[F:20])=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH:29](OCC)(OCC)OCC.[N-:39]=[N+:40]=[N-:41].[Na+]>CC(O)=O.CCOC(C)=O>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[C:15]4[CH2:27][C:26]5[C:21](=[CH:22][CH:23]=[C:24]([N:28]6[CH:29]=[N:41][N:40]=[N:39]6)[CH:25]=5)[C:16]=4[NH:17][C:18]=3[C:19]=2[F:20])=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 576185157-(4-Butylphenyl)-6-fluoro-5,10-dihydroindeno[1,2-b]indol-2-amine

Product 1

HCID 57618481HCID 57618481, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

7-(4-Butyl-phenyl)-6-fluoro-5,10-dihydro-indeno[1,2-b]indol-2-ylamine (example 98, step 1, 60 mg, 0.1620 mmol) is dissolved in AcOH (1.6 mL). Triethyl orthoformate (38 mg, 0.2591 mmol, 1.6 eq.) and sodium azide (15 mg, 0.2429 mmol, 1.5 eq.) are added to the starting material solution sequentially at room temperature. The resulting reaction mixture is heated to 80° C. for 3.5 h. After cooling to room temperature, the reaction is diluted with EtOAc and sequentially washed with H2O, 1 N HCl (aq), and saturated aqueous NaCl. The organic solution is dried over Na2SO4 and concentrated. The resulting residue is purified by reverse phase HPLC to afford the title compound as a tan solid: 1H NMR (400 MHz, Acetone-d6) δ 11.31 (bs, 1H), 9.77 (s, 1H), 8.15 (s, 1H), 7.97 (s, 2H), 7.62-7.52 (m, 3H), 7.38 (d, 2H), 7.21 (dd, 1H), 3.99 (s, 2H), 2.69 (t, 2H), 1.72-1.63 (m, 2H), 1.50-1.40 (m, 2H), 0.99 (t, 3H); ESMS m/z 424.1 (M+H+).

Workup

  1. customThe resulting reaction mixture
  2. temperatureAfter cooling to room temperature
  3. washsequentially washed with H2O, 1 N HCl (aq), and saturated aqueous NaCl
  4. dry with materialThe organic solution is dried over Na2SO4
  5. concentrationconcentrated
  6. customThe resulting residue is purified by reverse phase HPLC

Sources & evidence

ORD record
ord-26e2a3363ee74bccb263f7eadc42438c
Source dataset
uspto-grants-2012_04
Patent number
US08153671B2

Reaction notes

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