Sodium hydride → HCID 59279549, compound

HRID 1098157Notes

Reaction equation

HRID 1098157 reaction equation
[H-].[Na+].[OH:3][C@@H:4]([CH2:9][O:10][C@H:11]([CH3:15])[CH2:12][O:13][CH3:14])[C:5]([O:7][CH3:8])=[O:6].Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([C:26]3[C:31]([Cl:32])=[CH:30][CH:29]=[CH:28][N:27]=3)[N:24]=[CH:25][C:18]=12>C1COCC1.C(OCC)(=O)C>[Cl:32][C:31]1[C:26]([N:23]2[C:19]3=[N:20][CH:21]=[N:22][C:17]([O:3][C@@H:4]([CH2:9][O:10][C@H:11]([CH3:15])[CH2:12][O:13][CH3:14])[C:5]([O:7][CH3:8])=[O:6])=[C:18]3[CH:25]=[N:24]2)=[N:27][CH:28]=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 575044824-Chloro-1-(3-chloropyridin-2-YL)-1H-pyrazolo[3,4-D]pyrimidine2×HCID 59279561HCID 59279561, compound

Product 1

HCID 59279549HCID 59279549, compoundYield 55.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (62.4 mg, 1.56 mmol) was to (S)-methyl 2-hydroxy-3-((R)-1-methoxypropan-2-yloxy)propanoate (Intermediate Y6) (200 mg, 1.04 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting mixture was stirred for 10 minutes at 0° C. and then 4-chloro-1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B15) (360 mg, 1.35 mmol) was added and the reaction was allowed to warm up to room temperature and stirred for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL), and washed sequentially with water (10 mL) and saturated brine (5 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0-100% ethyl acetate in isohexane to afford the product (245 mg, 55.8%). 1H NMR (400 MHz, CDCl3) δ 1.19 (d, 3H), 3.33-3.48 (m, 5H), 3.74-3.82 (m, 4H), 4.13-4.18 (m, 2H), 5.81-5.86 (m, 1H), 7.43-7.48 (m, 1H), 7.98-8.02 (m, 1H), 8.39-8.41 (m, 1H), 8.58 (s, 1H), 8.60-8.63 (m, 1H); m/z (ESI+) (M+H)+=422.36; HPLC tR=1.93 min.

Workup

  1. temperatureto warm up to room temperature
  2. stirringstirred for 1 hour
  3. washwashed sequentially with water (10 mL) and saturated brine (5 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customevaporated
  6. customThe crude product was purified by flash silica chromatography
  7. washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-a312b0a99fb644f7aa5c909594ad0ea9
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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