Sodium hydride → HCID 59924802, compound

HRID 2300794Notes

Reaction equation

HRID 2300794 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4].[H-].[Na+].[C:16]1([C@@H:22]([NH:24][C:25]2[N:30]=[C:29](Cl)[CH:28]=[CH:27][N:26]=2)[CH3:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C>[C:16]1([C@@H:22]([NH:24][C:25]2[N:26]=[C:27]([N:11]3[C:7]4[CH:6]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[CH:13]=[CH:12][C:8]=4[N:9]=[CH:10]3)[CH:28]=[CH:29][N:30]=2)[CH3:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:16]1([C@@H:22]([NH:24][C:25]2[N:26]=[C:27]([N:9]3[C:8]4[CH:12]=[CH:13][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][C:7]=4[N:11]=[CH:10]3)[CH:28]=[CH:29][N:30]=2)[CH3:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2779733methyl 1H-1,3-benzodiazole-5-carboxylateHCID 59924636HCID 59924636, compound

Product 2

HCID 59924802HCID 59924802, compoundHCID 59924897HCID 59924897, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 5-methoxycarbonylbenzimidazole (66 mg, 0.375 mmol, 1 eq) in DMF (2 mL) was added NaH (15 mg, 0.375 mmol, 1 eq). The mixture was stirred until gas evolution ceased. To the DMF solution was added 2-[(S)-1-phenylethylamino]-4-chloro-pyrimidine (87.5 mg, 0.375 mmol, 1 eq). The mixture was heated to 80° C. and stirred for several hours. The DMF was removed under reduced pressure and the residue was diluted with ethyl acetate and washed with water. The aqueous layer was back extracted with ethyl acetate. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The product was purified by preparative thin layer chromatography (eluted with 7% MeOH in CH2Cl2) to give 30 mg 2-[(S)-1-phenylethylamino]-4-[6-(methoxycarbonyl)benzimidazol-1-yl]pyrimidine (faster regioisomer) and 26 mg 2-[(S)-1-phenylethylamino]-4-[5-(methoxycarbonyl)benzimidazol-1-yl]pyrimidine (slower regioisomer). 1H NMR (500 MHz, CD3OD): δ 1.58 (3H, d, J=7.5 Hz), 3.94 (3H, s), 4.59 (1H, br s), 5.1 (1H, br s) 6.97 (1H, d, J=5.5 Hz), 7.23 (1H, br t, J=7 Hz), 7.35 (2H, br m), 7.44 (2H, d, J=7.5 Hz), 7.6-8.1 (2H, m), 8.3-8.4 (2H, m), 8.91 (1H, br s). Mass spectrum (ESI) 374.2 (M+1).

Workup

  1. stirringstirred for several hours
  2. customThe DMF was removed under reduced pressure
  3. additionthe residue was diluted with ethyl acetate
  4. washwashed with water
  5. extractionThe aqueous layer was back extracted with ethyl acetate
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was purified by preparative thin layer chromatography (eluted with 7% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-b9d2ba2e258d49d5bc52ab7130f848eb
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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