Potassium Phosphate, Tribasic → HCID 71731272, compound

HRID 1056085Notes

Reaction equation

HRID 1056085 reaction equation
Cl[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[F:24][C:25]([F:31])([F:30])[C:26]1([NH2:29])[CH2:28][CH2:27]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(#N)C.[OH2:43]>>[C:26]([OH:21])([C:25]([F:31])([F:30])[F:24])=[O:43].[CH3:22][C:3]1[C:2]([NH:29][C:26]2([C:25]([F:31])([F:30])[F:24])[CH2:28][CH2:27]2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 116511961-(Trifluoromethyl)cyclopropanamine hydrochlorideHCID 18373917Acetonitrile--water (1/1)HCID 89783520HCID 89783520, compound

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 71731272HCID 71731272, compoundYield 14%

Conditions

Temperature
120 °C

Procedure

Prepared similarly to that described in Example 254 using 2-(3-chloro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 254c; 23 mg, 0.074 mmol), 1-(trifluoromethyl)cyclopropanamine hydrochloride (47.5 mg, 0.294 mmol, Astatech, Inc., Bristol, Pa.), Pd(tBu3P)2 (Strem, Newburyport, Mass.; 3.76 mg, 7.35 μmol), and K3PO4 (94 mg, 0.441 mmol), heating at 120° C. for 16 h. Purification by silica gel (100% DCM to 3% 2 M NH3 in MeOH/DCM) then by rpHPLC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% ACN/water with 0.1% TFA) provided 2-(2-methyl-3-((1-(trifluoromethyl)cyclopropyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (14% yield). MS (ESI, pos. ion) m/z: 402.2 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 1.29-1.33 (m, 2H) 1.58-1.62 (m, 2H) 2.62 (s, 3H) 2.95 (t, J=6.85 Hz, 2H) 3.66 (td, J=6.85, 2.54 Hz, 2H) 5.31 (br. s., 1H) 5.45 (s, 1H) 7.17 (d, J=2.15 Hz, 1H) 7.48 (t, J=7.63, 1 H) 7.71 (dd, J=8.12, 1.27 Hz, 1H) 7.99 (dd, J=7.53, 1.27 Hz, 1H) 12.47 (br. s., 1H). 19F NMR (376 MHz, DMSO-d6) δ ppm −72.08 (3F, s).

Workup

  1. customPrepared similarly to that
  2. customPurification by silica gel (100% DCM to 3% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-ae1374c7e48a4af9be6b822fbefc3bdd
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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