Tetrahydrofuran → 3-{5-Amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamide

HRID 646768Notes

Reaction equation

HRID 646768 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][CH:7]=1.C1COCC1.[NH2:15][C:16]1[C:17]([C:38](N(OC)C)=[O:39])=[N:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([NH:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:29])[CH:23]=2)=[CH:20][N:21]=1>O>[NH2:15][C:16]1[N:21]=[CH:20][C:19]([C:22]2[CH:23]=[C:24]([CH:25]=[CH:26][CH:27]=2)[C:28]([NH:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[O:29])=[N:18][C:17]=1[C:38]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)=[O:39]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 866078493-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamideHCID 178505773HCID 178505773, compound

Product 1

HCID 686511603-{5-Amino-6-[(3-fluorophenyl)carbonyl]pyrazin-2-yl}-N-(phenylmethyl)benzamideYield 4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-Fluorophenylmagnesium bromide (1.5 mL of a 0.5 M solution in TBF, 0.75 mmol) was added dropwise to a THF (10 mL) solution of 3-amino-6-{3-[(benzylamino)carbonyl]phenyl}-N-methoxy-N-methylpyrazine-2-carboxamide (0.10 g, 0.25 mmol) at 0° C. under N2. The reaction mixture was warmed to room temperature and stirred for 2 h. The mixture was diluted with water and extracted 3× with ethyl acetate. The combined organic layers were dried with magnesium sulfate, filtered, and concentrated under reduced pressure to give a yellow oil. The crude product was separated by preparative HPLC and lyophilized to give a yellow solid (4 mg, 4% yield). 1H NMR (400 MHz, d6-DMSO): δ 9.10 (t, 1H), 9.05 (s, 1H), 8.42 (bs, 1H), 8.01 (m, 2H), 7.86-7.80 (m, 2H), 7.74 (d, 1H), 7.57-7.51 (m, 2H), 7.47-7.43 (m, 2H), 7.38-7.32 (m, 2H), 7.28-7.24 (m, 2H), 6.47-6.59 (m, 1H), 4.50 (d, 2H). MS (EI) for C25H19FN4O2: 427 (MH+).

Workup

  1. extractionextracted 3× with ethyl acetate
  2. dry with materialThe combined organic layers were dried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give a yellow oil
  6. customThe crude product was separated by preparative HPLC

Sources & evidence

ORD record
ord-643f9c9a5b2c4f3f8bd621b273ad7174
Source dataset
uspto-grants-2010_04
Patent number
US07704995B2

Reaction notes

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