Diethylamine → HCID 57863428, compound

HRID 1446740Notes

Reaction equation

HRID 1446740 reaction equation
Cl.[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:25]4[CH:26]=[CH:27][C:28]([C:30]5[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][CH2:37][CH:38]=O)[CH:31]=5)=[CH:29][C:24]4=[N:23][CH:22]=3)=[CH:17][C:16]=2[F:40])=[O:13])[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].[CH2:41]([NH:43][CH2:44][CH3:45])[CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:25]4[CH:26]=[CH:27][C:28]([C:30]5[CH:35]=[CH:34][N:33]=[C:32]([CH2:36][CH2:37][CH2:38][N:43]([CH2:44][CH3:45])[CH2:41][CH3:42])[CH:31]=5)=[CH:29][C:24]4=[N:23][CH:22]=3)=[CH:17][C:16]=2[F:40])=[O:13])[CH:7]=1)([CH3:4])([CH3:3])[CH3:5]

Participants

5

Reactant 3

HCID 8021Diethylamine2×HCID 5049666Sodium triacetoxyborohydrideHCID 86634308HCID 86634308, compound

Product 1

HCID 57863428HCID 57863428, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Dissolve 1-(5-tert-butyl-isoxazol-3-yl)-3-(2-fluoro-4-{7-[2-(3-oxo-propyl)-pyridin-4-yl]-imidazo[1,2-a]pyridin-3-yl}-phenyl)-urea hydrochloride (0.5 g, 0.89 mmol) in acetic acid (20 mL) under nitrogen. Add diethylamine (0.46 mL, 5 equiv.) and stir overnight at room temperature. In the morning, add sodium triacetoxyborohydride (0.38 g, 2 equiv.) and stir 20 minutes. At this point add excess diethylamine and stir overnight at room temperature. Concentrate to dryness and purify by silica gel (10% Methanol:DCM) to give impure product. Purify by reverse phase (25% MeCN:0.03% HCl in water→100% MeCN). Dilute product containing fractions with ethyl acetate then wash with 1 N NaOH followed by aqueous saturated sodium chloride. Dry the organics over MgSO4, filter and concentrate to give the freebase (0.083 g, 16%) as a yellow solid. LCMS (ES), m/z 584.2 (M+1).

Workup

  1. stirringstir overnight at room temperature
  2. concentrationConcentrate to dryness
  3. custompurify by silica gel (10% Methanol:DCM)
  4. customto give impure product
  5. customPurify by reverse phase (25% MeCN:0.03% HCl in water→100% MeCN)
  6. additionDilute product containing fractions with ethyl acetate
  7. washthen wash with 1 N NaOH
  8. dry with materialDry the organics over MgSO4
  9. filtrationfilter
  10. concentrationconcentrate
  11. customto give the freebase (0.083 g, 16%) as a yellow solid

Sources & evidence

ORD record
ord-6c4a14a9eb114579a9cd44b2645bae30
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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