Sodium Cyanide → HCID 11691555, compound

HRID 1986631Notes

Reaction equation

HRID 1986631 reaction equation
N[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([N:12]([CH2:24][CH2:25][CH2:26][N:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=3)=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.N([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+].[C:44]([Cu])#[N:45].[C-]#N.[Na+]>Cl.O>[Cl:23][C:18]1[CH:17]=[C:16]([NH:15][C:13](=[O:14])[N:12]([CH:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:2]([C:44]#[N:45])=[CH:3][CH:4]=3)[CH2:9]2)[CH2:24][CH2:25][CH2:26][N:27]2[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]2)[CH:21]=[CH:20][C:19]=1[F:22]

Participants

8

Reactant 5

HCID 8929Sodium CyanideHCID 10340Sodium CarbonateHCID 23668193Sodium NitriteHCID 44417989HCID 44417989, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 11691555HCID 11691555, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(7-amino-1,2,3,4-tetrahydro-naphthalen-2-yl)-3-(3-chloro-4-fluoro-phenyl)-1-[3-(4-methyl-piperazin-1-yl)-propyl]-urea (from Preparative Example 27, 0.061 g, 0.13 mmol) in 18% aqueous HCl (0.077 mL) at 0° C. was added, slowly, a solution of NaNO2 (9.4 mg, 0.14 mmol) in H2O (0.091 mL) over 30 min. The mixture was neutralized with Na2CO3 (powder) followed by the addition of a solution of CuCN (0.012 g, 0.13 mmol) and NaCN (14 mg, 0.28 mmol) in H2O (0.091 mL). The mixture was then heated at 50° C. for 30 min. The reaction was concentrated in vacuo and the crude residue was purified on reverse-phase HPLC to give 0.015 g (24%) of 3-(3-chloro-4-fluoro-phenyl)-1-(7-cyano-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-[3-(4-methyl-piperazin-1-yl)-propyl]-urea as a white solid. 1H NMR (300 MHz, CD3OD): □ 7.59 (dd, 1H, J=6.6, 2.7 Hz), 7.50 (s, 1H), 7.46 (dd, 1H, J=8.1, 1.5 Hz), 7.34-7.26 (m, 2H), 7.16 (t, 1H, J=9.0 Hz), 4.31 (m, 1H), 3.55-3.35 (m, 10H), 3.15-3.00 (m, 6H), 2.92 (s, 3H), 2.05 (m, 4H). MS-ESI: 484.1 (M+H+).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe crude residue was purified on reverse-phase HPLC

Sources & evidence

ORD record
ord-b19c14cb85bb4218a6322e77e251ac94
Source dataset
uspto-grants-2009_06
Patent number
US07550467B2

Reaction notes

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