4-Cyanopiperidine → (R)-1-(2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoyl)piperidine-4-carbonitrile

HRID 1968241Notes

Reaction equation

HRID 1968241 reaction equation
[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13](O)=[O:14])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1.[NH:22]1[CH2:27][CH2:26][CH:25]([C:28]#[N:29])[CH2:24][CH2:23]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:16]([CH3:18])[CH3:17])[C:13]([N:22]3[CH2:27][CH2:26][CH:25]([C:28]#[N:29])[CH2:24][CH2:23]3)=[O:14])[C:8](=[O:19])[C:7]3=[CH:20][NH:21][C:5]([C:6]=23)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 1382234-CyanopiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67224695(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid

Product 1

HCID 49842252(R)-1-(2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoyl)piperidine-4-carbonitrileYield 25.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an 8 mL scintillation vial equipped for stirring was added (R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid (10 mg, 0.032 mmol). THF (0.5 mL), piperidine-4-carbonitrile (3.58 mg, 0.032 mmol) and HATU (14.83 mg, 0.039 mmol) were added and the solution was stirred at 25° C. for 1 h. The reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 5-50%). The fractions were collected, concentrated, and dried in vacuo to afford the title compound as a yellow oil (3.3 mg, 25.4%). 1H NMR (400 MHz, CD3OD) δ 0.84-0.93 (m, 3 H) 0.96-1.08 (m, 3 H) 1.42-1.60 (m, 1 H) 1.72-1.82 (m, 2 H) 1.82-2.00 (m, 1 H) 2.49-2.66 (m, 1 H) 2.92-3.07 (m, 1 H) 3.49-3.73 (m, 2 H) 3.78-4.00 (m, 1 H) 4.00-4.11 (m, 1 H) 4.90 (d, J=7.58 Hz, 1 H) 4.92-5.01 (m, 1 H) 5.53 (dd, J=10.86, 3.54 Hz, 1 H) 7.82-7.92 (m, 1 H) 8.15-8.30 (m, 1 H). [M+H] calc'd for C20H22ClN5O2, 400; found, 400.4.

Workup

  1. customTo an 8 mL scintillation vial equipped
  2. stirringthe solution was stirred at 25° C. for 1 h
  3. customThe reaction mixture was purified via preparative mass trigger LC-MS (AcCN/H2O, 5-50%)
  4. customThe fractions were collected
  5. concentrationconcentrated
  6. customdried in vacuo

Sources & evidence

ORD record
ord-a3c9c40f7bc34f2dbfe8a41371400788
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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