Butyl nitrite → 6-benzenesulfonyl-1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene

HRID 1257577Notes

Reaction equation

HRID 1257577 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH2:33])[C:18]([NH:19][C@@H:20]4[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:34](OCCCC)=O>C(#N)C.[Cu](Br)Br>[C:1]1([S:7]([N:10]2[CH:11]=[CH:12][C:13]3[C:14]2=[N:15][CH:16]=[C:17]2[C:18]=3[N:19]([C@@H:20]3[CH2:25][CH2:24][CH2:23][N:22]([CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:21]3)[N:34]=[N:33]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 10996Butyl nitriteHCID 583947461-benzenesulfonyl-N*4*-((R)-1-benzyl-piperidin-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine

Product 1

HCID 583952996-benzenesulfonyl-1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indaceneYield 65.1%

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A stirred solution of 1-benzenesulfonyl-N*4*-((R)-1-benzyl-piperidin-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine (300 mg, 0.65 mmol) in acetonitrile (6 ml) was treated with copper (II) bromide (174 mg, 0.78 mmol) and n-butyl nitrite (114 μl, 0.97 mmol) and then heated to 70° C. for 2 hours. After cooling, the reaction was quenched by the addition of 1M aqueous HCl solution (ca. 5 ml) and stirred for 5 minutes. The mixture was basified with saturated sodium hydrogen carbonate solution and extracted with ethyl acetate (3×). The combined extracts were washed with brine, dried with sodium sulfate and concentrated under vacuum to leave a brown residue. Purification by column chromatography on silica gel (gradient: 0 to 60% ethyl acetate in cyclohexane) gave 200 mg (65%) of 6-benzenesulfonyl-1-((R)-1-benzyl-piperidin-3-yl)-1,6-dihydro-1,2,3,5,6-pentaaza-as-indacene as a brown residue. LCMS (Method B, ESI): RT=3.38 min, m+H=473.5; 1H NMR (400 MHz, CDCl3) δ: 9.18 (s, 1H), 8.21 (m, 2H), 7.82 (d, 1H), 7.57 (m, 1H), 7.53-7.46 (m, 2H), 7.30 (s, 5H), 6.75 (d, 1H), 4.88 (m, 1H), 3.61 (dd, 2H), 3.25 (m, 1H), 3.03 (m, 1H), 2.57 (m, 1H), 2.39-2.17 (m, 3H), 2.10-1.87 (m, 2H).

Workup

  1. temperatureAfter cooling
  2. customthe reaction was quenched by the addition of 1M aqueous HCl solution (ca. 5 ml)
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto leave a brown residue
  8. customPurification by column chromatography on silica gel (gradient: 0 to 60% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-f5540cbfd9ba45e2a56f17456735847a
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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