Water → HCID 178521005, compound

HRID 931276Notes

Reaction equation

HRID 931276 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:15])[CH2:9]2)[CH:5]=[CH:4][C:3]=1[N+:21]([O-])=O.[CH:24]1([C:27]2[N:32]=[C:31]([CH:33]=O)[CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25]1.S(S([O-])=O)([O-])=O.[Na+].[Na+].O>C(O)C>[CH:24]1([C:27]2[N:32]=[C:31]([C:33]3[NH:1][C:2]4=[N:7][C:6]([N:8]5[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([N:16]6[CH2:20][CH2:19][CH2:18][CH2:17]6)=[O:15])[CH2:9]5)=[CH:5][CH:4]=[C:3]4[N:21]=3)[CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 962WaterHCID 24489Sodium DithioniteHCID 193617216-CyclopropylpicolinaldehydeHCID 89853768(R)-(1-(6-amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone

Product 1

HCID 178521005HCID 178521005, compoundYield 18.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (R)-(1-(6-amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone (250 mg, 0.711 mmol) in ethanol (15 mL) was added 6-cyclopropylpicolinaldehyde (0.137 g, 0.974 mmol), sodium dithionite (536 mg, 2.96 mmol) and water (2 mL). The reaction mixture was stirred for 16 h at 100° C. in a sealed tube. The mixture was cooled, and the solvent was removed under reduced pressure. Water was added to the residue and the mixture was extracted with ethyl acetate. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via preparative TLC eluting with 4% methanol in dichloromethane to afford the title compound (55 mg, 17%). MS (ES+APCI) (M+H) 417.2; LCMS retention time 1.944 (Method F). 1H NMR (300 MHz, CDCl3) δ 1.00-1.09 (m, 2H), 1.09-1.16 (m, 2H), 1.63-1.74 (m, 1H), 1.81-2.14 (m, 7H), 2.62-2.76 (m, 1H), 2.99 (dd, 1H), 3.08-3.21 (m, 1H), 3.44-3.55 (m, 3H), 3.58-3.70 (m, 1H), 4.35 (d, 1H), 4.48 (d, 1H), 6.71 (d, 1H), 7.19 (d, 1H), 7.66 (t, 1H), 7.87 (d, 1H), 8.04 (d, 1H), 10.18 (br s, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. customthe solvent was removed under reduced pressure
  3. additionWater was added to the residue
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via preparative TLC
  9. washeluting with 4% methanol in dichloromethane

Sources & evidence

ORD record
ord-c3152e73180d4b9b915afd911fcab018
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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