Cyanoacetic acid → HCID 86708608, compound

HRID 921726Notes

Reaction equation

HRID 921726 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([Cl:28])=[C:7]([NH:13][C:14]3[N:19]=[C:18]([NH:20][CH2:21][CH3:22])[C:17]4=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:16]4[N:15]=3)[CH:8]=[C:9]([C:11]#[N:12])[CH:10]=2)[CH2:2]1.[C:29]([CH2:31][C:32](O)=[O:33])#[N:30].Cl.CN(C)CCCN=C=NCC.C1C=C2N=NN(O)C2=CC=1.O.C([O-])(=O)C.[NH4+]>CN1C(=O)CCC1.CO.O>[Cl:28][C:6]1[C:5]([CH:3]2[CH2:2][N:1]([C:32](=[O:33])[CH2:31][C:29]#[N:30])[CH2:4]2)=[CH:10][C:9]([C:11]#[N:12])=[CH:8][C:7]=1[NH:13][C:14]1[N:19]=[C:18]([NH:20][CH2:21][CH3:22])[C:17]2=[N:23][CH:24]=[C:25]([C:26]#[N:27])[N:16]2[N:15]=1

Participants

9

Reactant 5

HCID 9740Cyanoacetic acidHCID 517165Ammonium AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86708607HCID 86708607, compound

Product 1

HCID 86708608HCID 86708608, compoundYield 20.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-((3-(azetidin-3-yl)-2-chloro-5-cyanophenyl)amino)-4-(ethylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (15 mg, 0.038 mmol), 2-cyanoacetic acid (4.9 mg, 0.057 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.4 mg, 0.065 mmol), and HOBT monohydrate (9.9 mg, 0.065 mmol) in NMP (1 mL) was stirred at room temperature for 4 hr. Preparative HPLC (Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: water; Mobile Phase B: methanol; Buffer: 20-mM ammonium acetate; Gradient: 30-95% B over 19.5 minutes, then a 14.0 minute hold at 95% B; Flow: 20 mL/min) afforded the title compound (3.6 mg). This was converted to the mono HCl salt.

Workup

  1. waitGradient: 30-95% B over 19.5 minutes
  2. customa 14.0 minute hold

Sources & evidence

ORD record
ord-df56747d160c4c2f91746a6e9af4d3f7
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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