Aminoacetonitrile → (R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-N-(cyanomethyl)-3-methylbutanamide

HRID 1968239Notes

Reaction equation

HRID 1968239 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][CH2:23][C:24]#[N:25].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]([NH:25][CH2:24][C:23]#[N:22])=[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 10901AminoacetonitrileHCID 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 49842139(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-N-(cyanomethyl)-3-methylbutanamideYield 34.3%

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), 2-aminoacetonitrile (3.64 mg, 0.065 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 (3.8 mg, 33.8%). 1H NMR (400 MHz, CD3OD) δ 0.85-0.97 (m, 3 H) 1.02 (d, J=6.57 Hz, 1 H) 1.07 (d, J=6.32 Hz, 2 H) 2.53 (dt, J=11.18, 6.54 Hz, 1 H) 3.52-3.86 (m, 2 H) 4.89-5.04 (m, 1 H) 5.07 (d, J=11.37 Hz, 1 H) 5.51 (d, J=10.86 Hz, 1 H) 7.80-7.89 (m, 1 H) 8.13-8.34 (m, 1 H). [M+H] calc'd for C16H16ClN5O2, 346; found, 346.4.

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-9752c0417a5d4799a6151618ad61fb6c
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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