Sodium hydride → HCID 57504380, compound

HRID 1098014Notes

Reaction equation

HRID 1098014 reaction equation
[H-].[Na+].[OH:3][C@@H:4]([CH2:15][O:16][C@@H:17]([CH3:21])[CH2:18][O:19][CH3:20])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].Cl[C:23]1[N:28]=[CH:27][N:26]=[C:25]2[N:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[Cl:38])[N:30]=[CH:31][C:24]=12>C1COCC1.C(OCC)(=O)C>[Cl:38][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[N:29]1[C:25]2=[N:26][CH:27]=[N:28][C:23]([O:3][C@@H:4]([CH2:15][O:16][C@@H:17]([CH3:21])[CH2:18][O:19][CH3:20])[C:5]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=3)=[O:6])=[C:24]2[CH:31]=[N:30]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2×HCID 57504508HCID 57504508, compound2×

Product 1

HCID 57504380HCID 57504380, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (21.24 mg, 0.53 mmol) was added to (S)-2-hydroxy-3-((S)-1-methoxypropan-2-yloxy)-N-(5-methylpyridin-2-yl)propanamide (Intermediate Y5) (95 mg, 0.35 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (122 mg, 0.46 mmol) in dry THF (2 mL) was added. 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 (160 mg, 91%). 1H NMR (400 MHz, DMSO) δ 1.09 (d, 3H), 2.24 (s, 3H), 3.23 (s, 3H), 3.26-3.38 (m, 2H), 3.77-3.86 (m, 1H), 4.00-4.16 (m, 2H), 5.85-5.91 (m, 1H), 7.55-7.70 (m, 4H), 7.73-7.78 (m, 1H), 7.88 (d, 1H), 8.16-8.19 (m, 1H), 8.54 (s, 1H), 8.59 (s, 1H), 10.79 (s, 1H). m/z (ESI+) (M+H)+=497.20; HPLC tR=2.36 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-bb403f6ce67d4a5ab7a7c7fc417e679b
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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