Benzylamine → HCID 68650855, compound

HRID 646681Notes

Reaction equation

HRID 646681 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16]([OH:18])=O)=[N:6][C:7]=1[C:8]([NH:10][CH2:11][CH3:12])=[O:9].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[CH2:39]([NH2:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([C:8]([NH:10][CH2:11][CH3:12])=[O:9])=[N:6][C:5]([C:13]2[CH:21]=[CH:20][CH:19]=[C:15]([C:16]([NH:46][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[O:18])[CH:14]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 68650663HCID 68650663, compound

Product 1

HCID 68650855HCID 68650855, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoate (480 mg, 1.6 mmol) was suspended in a 20 mL of 1:1 MeOH-5% aqueous sodium hydroxide and heated at 90-95° C. for 4 hours. The homogeneous reaction mixture was cooled to room temperature, concentrated to half the initial volume, cooled in an ice-bath, and acidified to pH of 4 with concentrated HCl. A white solid precipitated and was collected, washed with water and dried in vacuo to give 3-{5-amino-6-[(ethylamino)carbonyl]pyrazin-2-yl}benzoic acid (445 mg, 97% yield). The pyrazine acid (40 mg, 0.14 mmol) was dissolved in DMF (1 mL), and then 1-hydroxybenzotriazole (30 mg, 0.22 mmol), 1-[(3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (30 mg, 0.16 mmol), and 4-methylmorpholine (30 mg, 0.28 mol) were added sequentially. After one hour benzylamine (30 mg, 0.27 mmol) was added to the reaction mixture and stirring was continued at room temperature for 18 hours. The mixture was then diluted with ethyl acetate (10 mL), washed with water, saturated sodium bicarbonate solution then brine and dried over sodium sulfate, filtered, and concentrated. The oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield) to give 3-amino-N-ethyl-6-(3-{[(phenylmethyl)amino]carbonyl}phenyl)pyrazine-2-carboxamide (a tan color solid, 22 mg, 42% yield): 1H NMR (400 MHz, DMSO-d6): 9.14 (s, 1H), 8.88 (s, 1H), 8.87-8.85 (b, 1H), 8.51 (s, 1H), 8.37-8.34 (d, 1H), 7.87-7.85 (d, 1H), 7.63-7.59 (b, 1H), 7.58-7.54 (t, 1), 7.34-7.23 (m, 4H), 4.53-4.52 (d, 2H), 3.38-3.29 (m, 2H), 1.171.14 (t, 3H); MS (EI) for C21H21N5O2: 376 (MH+).

Workup

  1. washwashed with water, saturated sodium bicarbonate solution
  2. dry with materialbrine and dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe oily residue was purified by flash chromatography (silica gel, eluted with ethyl acetate-hexanes gradient from 15% to 80% yield)

Sources & evidence

ORD record
ord-5f8ab7b82b2b4175b7f26f72e2179fb3
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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