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

HRID 1968242Notes

Reaction equation

HRID 1968242 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:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=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]([NH:22][C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][CH:24]=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 133964-AminobenzonitrileHCID 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 49842140(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-N-(4-cyanophenyl)-3-methylbutanamideYield 15.3%

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), 4-aminobenzonitrile (7.68 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 (2 mg, 15.1%). 1H NMR (400 MHz, CD3OD) δ 0.90-1.03 (m, 3 H) 1.07-1.15 (m, 3 H) 2.59 (dt, J=11.24, 6.63 Hz, 1 H) 5.01 (d, J=19.45 Hz, 1 H) 5.21 (d, J=11.12 Hz, 1 H) 5.42 (d, J=19.45 Hz, 1 H) 7.64-7.66 (m, 1 H) 7.66-7.68 (m, 1 H) 7.80-7.82 (m, 1 H) 7.82-7.84 (m, 1 H) 7.86 (s, 1 H) 8.25 (s, 1 H). [M+H] calc'd for C21H18ClN5O2, 408; found, 408.4.

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-9b43f4644b564a908a85ed8333c17703
Source dataset
uspto-grants-2013_04
Patent number
US08420816B2

Reaction notes

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