Ethyl orthoformate → HCID 67344361, compound

HRID 1257641Notes

Reaction equation

HRID 1257641 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:34]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:22][CH:21]4[CH3:33])=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OCC)(OCC)[O:38][CH2:39][CH3:40]>C(O)(=O)C.[Fe]>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH:34][C:39](=[O:38])[CH3:40])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:22][CH:21]4[CH3:33])=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 31214Ethyl orthoformateHCID 67345125HCID 67345125, compound

Product 1

HCID 67344361HCID 67344361, compoundYield 10.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of racemic (1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-yl)-(1-benzyl-3-methyl-piperidin-4-yl)-amine (1.88 g, 3.7 mmol), iron powder (1.68 g, 30.0 mmol) and triethyl orthoformate (1.66 mL, 10.0 mmol) in acetic acid (20 mL) were heated at 100° C. for 1 hour. The cooled reaction mixture was filtered through Celite® and the filtrate concentrated under vacuum. The resulting residue was dissolved in ethyl acetate and the organic phase washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate and concentrated under vacuum. The resulting residue was purified by column chromatography on silica gel (gradient: 0 to 3% methanol in DCM) to afford 822 mg (46%) of racemic cis 6-benzenesulfonyl-1-(1-benzyl-3-methyl-piperidin-4-yl)-1,6-dihydro-1,2,3,5,6-tetraaza-as-indacene, 523 mg (29%) of racemic trans 6-benzenesulfonyl-1-(1-benzyl-3-methyl-piperidin-4-yl)-1,6-dihydro-1,2,3,5,6-tetraaza-as-indacene and 203 mg (10%) of N-[1-benzenesulfonyl-4-(1-benzyl-3-methyl-piperidin-4-yl amino)-1H-pyrrolo[2,3-b]pyridin-5-yl]-acetamide. Analysis for racemic cis 6-benzenesulfonyl-1-(1-benzyl-3-methyl-piperidin-4-yl)-1,6-dihydro-1,2,3,5,6-tetraaza-as-indacene: LCMS (Method I, ESI): RT=2.33 min, m+H=486.3; 1H NMR (400 MHz, CDCl3) δ: 8.92 (s, 1H), 8.26-8.21 (m, 2H), 7.96 (s, 1H), 7.80 (d, 1H), 7.56-7.44 (m, 3H), 7.35-7.32 (m, 4H), 7.29-7.24 (m, 1H), 6.70 (d, 1H), 4.64 (dt, 1H), 3.62 (d, 1H), 3.52 (d, 1H), 3.20-3.09 (m, 1H), 2.88 (m, 1H), 2.60 (m, 1H), 2.48-2.38 (m, 2H), 2.27 (td, 1H), 2.04 (s, 1H), 0.83 (d, 3H). Analysis for racemic trans 6-benzenesulfonyl-1-(1-benzyl-3-methyl-piperidin-4-yl)-1,6-dihydro-1,2,3,5,6-tetraaza-as-indacene: LCMS (Method I, ESI): RT=2.37 min, m+H=486.3; 1H NMR (400 MHz, CDCl3) δ: 8.91 (s, 1H), 8.26 (m, 2H), 8.05-7.96 (br s, 1H), 7.87-7.77 (br s, 1H), 7.50 (m, 3H), 7.35 (m, 4H), 7.30 (m, 1H), 6.79 (br s, 1H), 4.05 (br s, 1H), 3.60 (s, 2H), 3.14-3.04 (m, 3H), 2.40-1.85 (m, 3H), 1.63-1.54 (m, 1H), 0.78-0.66 (m, 3H). Analysis for N-[1-Benzenesulfonyl-4-(1-benzyl-3-methyl-piperidin-4-ylamino)-1H-pyrrolo[2,3-b]pyridin-5-yl]-acetamide: LCMS (Method I, ESI): RT=2.26 min, m+H=518.3; 1H NMR (400 MHz, CDCl3) δ: 8.19-8.12 (m, 1H), 8.08 (d, 2H), 7.84 (s, 1H), 7.79 (s, 1H), 7.59-7.37 (m, 5H), 7.33-7.26 (m, 3H), 6.52 (d, 1H), 3.89 (s, 1H), 3.56 (m, 2H), 2.48-2.37 (m, 3H), 2.20 (s, 3H), 2.04 (s, 3H), 1.82-1.77 (m, 2H), 0.95-0.89 (m, 3H).

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered through Celite®
  3. concentrationthe filtrate concentrated under vacuum
  4. dissolutionThe resulting residue was dissolved in ethyl acetate
  5. washthe organic phase washed with saturated aqueous sodium bicarbonate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe resulting residue was purified by column chromatography on silica gel (gradient: 0 to 3% methanol in DCM)

Sources & evidence

ORD record
ord-d7109fd70a4b49069aad09512ea39e17
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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