Sodium hydride → (S)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

HRID 1844370Notes

Reaction equation

HRID 1844370 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]4[CH:25]=[CH:24]C([N+]([O-])=O)=C[CH:21]=4)=[O:18])[CH2:13][CH2:12]3)=[N:7][C:6]=12.[O:29]1CC[C@H](O)C1.[H-].[Na+]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C@H:20]4[CH2:25][CH2:24][O:29][CH2:21]4)=[O:18])[CH2:13][CH2:12]3)=[N:7][C:6]=12

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 866974514-Nitrophenyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Product 1

HCID 86697456(S)-tetrahydrofuran-3-yl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylateYield 151.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 224 mg (0.50 mmol) of 4-nitrophenyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate dissolved in 18 mL of THF, was added (S)-tetrahydrofuran-3-ol (88 mg, 1.0 mmol), followed by 60% NaH (80 mg, 2.0 mmol) and stirred at RT for 2 hr. After 2 hr it was diluted with 30 mL of EtOAc and slowly quench with brine. The organic layer was dried over MgSO4 and concentrated, it was purified using a 40 g silica gel column eluting with 0-10% MeOH/DCM to obtain 301 mg (76% yield) of the desired product. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.01-2.13 (m, 1 H) 2.17-2.29 (m, 1 H) 3.57-3.70 (m, 4 H) 3.74-3.84 (m, 4 H) 3.86-4.01 (m, 4 H) 5.27-5.38 (m, 1 H) 6.37 (d, J=7.83 Hz, 1 H) 7.87 (s, 1 H) 8.28 (d, J=7.83 Hz, 1 H)

Workup

  1. customslowly quench with brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. customit was purified
  5. washeluting with 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-2c2a318560a34485974eedab17b8e6db
Source dataset
uspto-grants-2015_02
Patent number
US08946415B2

Reaction notes

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