Sodium hydride → HCID 57504497, compound

HRID 1098005Notes

Reaction equation

HRID 1098005 reaction equation
[H-].[Na+].[CH:3]1([O:7][CH2:8][C@H:9]([OH:20])[C:10]([NH:12][C:13]2[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=2)=[O:11])[CH2:6][CH2:5][CH2:4]1.Cl[C:22]1[N:27]=[CH:26][N:25]=[C:24]2[N:28]([C:31]3[CH:36]=[CH:35][N:34]=[CH:33][C:32]=3[CH3:37])[N:29]=[CH:30][C:23]=12>C1COCC1>[CH:3]1([O:7][CH2:8][C@H:9]([O:20][C:22]2[C:23]3[CH:30]=[N:29][N:28]([C:31]4[CH:36]=[CH:35][N:34]=[CH:33][C:32]=4[CH3:37])[C:24]=3[N:25]=[CH:26][N:27]=2)[C:10]([NH:12][C:13]2[CH:18]=[N:17][C:16]([CH3:19])=[CH:15][N:14]=2)=[O:11])[CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 57438646HCID 57438646, compoundHCID 57504623HCID 57504623, compound

Product 1

HCID 57504497HCID 57504497, compoundYield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

60% Sodium hydride in mineral oil (48.8 mg, 1.22 mmol) was added in one portion to (S)-3-cyclobutoxy-2-hydroxy-N-(5-methylpyrazin-2-yl)propanamide (Intermediate R1) (205 mg, 0.81 mmol) in anhydrous THF (5 mL) cooled to 0° C. under nitrogen. The resulting suspension was stirred at 0° C. for 10 minutes and then 4-chloro-1-(3-methylpyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate M1) (200 mg, 0.81 mmol) as suspension in dry THF (4 mL) added dropwise over 1 minute. The mixture was stirred at 0° C. for 15 mins, allowed to warm slowly to ambient temperature and stirred for 2 hours. 1M Citric mins, allowed to warm slowly to ambient temperature and stirred for 2 hours. 1M Citric combined organic extracts were washed with water (15 mL) and brine (15 mL), dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 10% MeOH in ethyl acetate to give the product (360 mg, 96%). 1H NMR (400 (2H, m), 2.35 (3H, s), 2.54 (3H, s), 3.97-4.10 (3H, m), 6.05 (1H, t), 7.49 (1H, d), 8.12 (1H, d), 8.44 (1H, s), 8.61 (1H, s), 8.62-8.65 (2H, m), 8.69 (1H, s), 9.44 (1H, d); m/z (ESI+) (M+H)+=461; HPLC tR=1.67 min.

Workup

  1. stirringThe mixture was stirred at 0° C. for 15 mins
  2. temperatureto warm slowly to ambient temperature
  3. stirringstirred for 2 hours
  4. temperatureto warm slowly to ambient temperature
  5. stirringstirred for 2 hours
  6. washwere washed with water (15 mL) and brine (15 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was purified by flash silica chromatography
  10. washeluting (MgSO4)
  11. customevaporated
  12. customThe residue was purified by flash silica chromatography
  13. washeluting with 0 to 10% MeOH in ethyl acetate

Sources & evidence

ORD record
ord-352ecb79a74c435baa6c1af430c283be
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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