Benzylamine → HCID 54597091, compound

HRID 2174649Notes

Reaction equation

HRID 2174649 reaction equation
Br[C:2]1[C:3]([NH2:20])=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH:17]([CH3:19])[CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[N:7]=1.[CH2:21](N)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C[CH2:30][N:31](CC)CC>CN1C(=O)CCC1.O>[CH:17]([S:14]([C:11]1[CH:12]=[CH:13][C:8]([C:6]2[N:7]=[C:2]([NH:31][CH2:30][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:3]([NH2:20])=[N:4][CH:5]=2)=[CH:9][CH:10]=1)(=[O:16])=[O:15])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 7504Benzylamine2×HCID 8471TriethylamineHCID 580843723-Bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine

Product 1

HCID 54597091HCID 54597091, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-bromo-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine (50 mg, 0.1404 mmol), benzylamine (30.09 mg, 30.67 μL, 0.2808 mmol) and Et3N (28.41 mg, 39.13 μL, 0.2808 mmol) in NMP (500 μL) were heated at 120° C. under microwave conditions for 1.5 hours. A further portion of benzylamine (225.7 mg, 230.1 μL, 2.106 mmol) was added and the reaction heated at 120° C. under microwave conditions for a further 45 minutes. The reaction mixture was diluted with water and extracted with EtOAc (×3). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a cream solid (22.3 mg, 42% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.16 (d, 6H), 3.41 (sept, 1H), 4.70 (d, 2H), 7.15 (br s, 1H), 7.26 (t, 1H), 7.36 (t, 2H), 7.44 (d, 2H), 7.82 (d, 2H), 7.96 (s, 1H) and 8.14 (d, 2H) ppm; MS (ES+) 383.2.

Workup

  1. temperaturethe reaction heated at 120° C. under microwave conditions for a further 45 minutes
  2. extractionextracted with EtOAc (×3)
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  7. customThe fractions were collected
  8. customfreeze-dried

Sources & evidence

ORD record
ord-10e7664b8c064bc0b90e51a77f667083
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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