Lithium Hexamethyldisilazide → HCID 57504324, compound

HRID 1097988Notes

Reaction equation

HRID 1097988 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[OH:11][C@@H:12]([CH2:22][O:23][CH3:24])[C:13]([NH:15][C:16]1[S:20][N:19]=[C:18]([CH3:21])[N:17]=1)=[O:14].Cl[C:26]1[N:31]=[CH:30][N:29]=[C:28]2[N:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[Cl:41])[N:33]=[CH:34][C:27]=12>C1COCC1.CCOC(C)=O>[Cl:41][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=1[N:32]1[C:28]2=[N:29][CH:30]=[N:31][C:26]([O:11][C@@H:12]([CH2:22][O:23][CH3:24])[C:13]([NH:15][C:16]3[S:20][N:19]=[C:18]([CH3:21])[N:17]=3)=[O:14])=[C:27]2[CH:34]=[N:33]1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 112655704-Chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-D]pyrimidine2×HCID 57504481HCID 57504481, compound2×

Product 1

HCID 57504324HCID 57504324, compoundYield 11.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of lithium bis(trimethylsilyl)amide (0.947 mL, 0.95 mmol) was added dropwise to a stirred solution of (S)-2-hydroxy-3-methoxy-N-(3-methyl-1,2,4-thiadiazol-5-yl)propanamide (Intermediate E1) (187 mg, 0.86 mmol) in anhydrous THF (5 mL) over a period of 3 minutes under nitrogen. The resulting suspension was stirred at ambient temperature for 10 minutes and then a solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (228 mg, 0.86 mmol) in dry THF (1.5 mL) added dropwise over 1 minute and the reaction heated to 50° C. for 16 hours. Reaction was cooled, diluted with EtOAc (50 mL), washed with 1M citric acid (25 mL) and brine (25 mL), dried (MgSO4), and evaporated. The residue was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane to afford (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-methoxy-N-(3-methyl-1,2,4-thiadiazol-5-yl)propanamide (44 mg, 11%) 1H NMR (400 MHz, CDCl3) δ 2.48 (3H, s), 3.41 (3H, s), 4.01 (2H, ddd), 6.13 (1H, t), 7.38-7.48 (3H, m), 7.56 (1H, dd), 8.34 (1H, s), 8.51 (1H, s), 9.90 (1H, s). m/z (ESI+) (M+H)+=446.08; HPLC tR=2.02 min.

Workup

  1. temperaturethe reaction heated to 50° C. for 16 hours
  2. customReaction
  3. temperaturewas cooled
  4. washwashed with 1M citric acid (25 mL) and brine (25 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-9a56ba2f93ec413580b17d01528f5e7e
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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