Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-N-((R)-1-cyanobutan-2-yl)-3-methylbutanamide

HRID 1627149Notes

Reaction equation

HRID 1627149 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.[NH2:22][C@H:23]([CH2:27][CH3:28])[CH2:24][C:25]#[N:26].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]([CH3:17])[CH3:18])[C:13]([NH:22][C@H:23]([CH2:27][CH3:28])[CH2:24][C:25]#[N:26])=[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 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 98988043-Aminopentanenitrile, (3R)-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 49842255(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-N-((R)-1-cyanobutan-2-yl)-3-methylbutanamideYield 23.4%

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), (R)-3-aminopentanenitrile (3.19 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 (2.9 mg, 23.01%). 1H NMR (400 MHz, CD3OD) δ 0.82 (t, J=7.45 Hz, 3 H) 0.89-0.99 (m, 3 H) 1.11 (d, J=6.57 Hz, 3 H) 1.44-1.68 (m, 2 H) 2.41-2.56 (m, 1 H) 2.63 (dd, J=16.93, 7.33 Hz, 1 H) 2.76 (dd, J=16.93, 5.05 Hz, 1 H) 3.99 (d, J=10.61 Hz, 1 H) 4.95 (d, J=19.96 Hz, 1 H) 5.05 (d, J=11.37 Hz, 1 H) 5.35 (d, J=19.71 Hz, 1 H) 7.85 (s, 1 H) 8.20-8.27 (m, 1 H). [M+H] calc'd for C19H22ClN5O2, 388; found, 388.4.

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-52b6d823298643a8a3a237d0ba93b617
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

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