Water → 5-(1-aminoethyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 2369020Notes

Reaction equation

HRID 2369020 reaction equation
[N:1]([CH:4]([C:6]1[CH:11]=[C:10]([N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]2[N:29]=[CH:30][C:31]([C:32]3[CH:33]=[N:34][C:35]4[C:40]([CH:41]=3)=[CH:39][C:38]([F:42])=[CH:37][CH:36]=4)=[C:8]2[N:7]=1)[CH3:5])=[N+]=[N-].C1COCC1.CP(C)C.O>CCOC(C)=O>[NH2:1][CH:4]([C:6]1[CH:11]=[C:10]([N:12]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:19])[CH3:20])[N:9]2[N:29]=[CH:30][C:31]([C:32]3[CH:33]=[N:34][C:35]4[C:40]([CH:41]=3)=[CH:39][C:38]([F:42])=[CH:37][CH:36]=4)=[C:8]2[N:7]=1)[CH3:5]

Participants

6

Reactant 4

HCID 962WaterHCID 8028Tetrahydrofuran2×HCID 68983TrimethylphosphineHCID 86664796HCID 86664796, compound

Product 1

HCID 665845645-(1-aminoethyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amineYield 82%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(1-azidoethyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (6.2 g, 10.3 mmol) and THF (90 mL) was added 1M trimethylphosphine in THF (30.8 mL, 30.8 mmol) dropwise. After 30 minutes the reaction was complete by HPLC. Water (30 mL) was therefore added and the reaction stirred an additional hour. The contents of the flask were transferred to a separatory funnel, diluted with 300 mL of EtOAc and washed three times with water and three times with brine. The organics were dried over sodium sulfate, filtered and concentrated in vacuo. Purified the remaining crude material by flash chromatography (0-2% 0.7N NH3 in MeOH/CHCl3) to afford 5-(1-aminoethyl)-3-(6-fluoroquinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (4.9 g, 82% yield) as a yellow solid. HPLC: 6.62 min (Method C). LCMS:ESI+ m/z of 583 (M+H)

Workup

  1. customThe contents of the flask were transferred to a separatory funnel
  2. washwashed three times with water and three times with brine
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurified the remaining crude material by flash chromatography (0-2% 0.7N NH3 in MeOH/CHCl3)

Sources & evidence

ORD record
ord-34d5981ed57d410eb1dbfdb892f6bf3d
Source dataset
uspto-grants-2014_04
Patent number
US08703784B2

Reaction notes

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