Triethylamine → HCID 57863459, compound

HRID 1446730Notes

Reaction equation

HRID 1446730 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:12]=[CH:11][N:10]3[C:13]([C:16]4[CH:21]=[CH:20][C:19]([NH2:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=4)=[CH:14][N:15]=[C:9]3[CH:8]=2)=[CH:3][CH:2]=1.C(N(CC)CC)C.ClC(Cl)(O[C:38](=[O:44])OC(Cl)(Cl)Cl)Cl.[C:46]([C:50]1[O:54][N:53]=[C:52]([NH2:55])[CH:51]=1)([CH3:49])([CH3:48])[CH3:47]>C(Cl)Cl>[C:46]([C:50]1[O:54][N:53]=[C:52]([NH:55][C:38]([NH:22][C:19]2[CH:20]=[CH:21][C:16]([C:13]3[N:10]4[CH:11]=[CH:12][C:7]([C:4]5[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=5)=[CH:8][C:9]4=[N:15][CH:14]=3)=[CH:17][C:18]=2[C:23]([F:26])([F:25])[F:24])=[O:44])[CH:51]=1)([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 68543253HCID 68543253, compound

Product 1

HCID 57863459HCID 57863459, compoundYield 144.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve 4-(7-pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-2-trifluoromethyl-phenylamine (0.4 g, 1.1 mmol) in DCM (40 mL) under nitrogen. Add triethylamine (0.39 mL, 2.5 equiv.) followed by careful addition of triphosgene (0.13 g, 0.4 equiv.). After 15 minutes at room temperature, add 5-tert-butyl-isoxazol-3-ylamine (0.19 g, 1.2 equiv.) and stir for 2 days at room temperature. Quench with water then dilute with ethyl acetate. Wash organics with 1 N NaOH followed by aqueous saturated sodium chloride. Dry organics over MgSO4 then filter and concentrate. Purify by reverse phase (5% MeCN:0.03% HCl in water→65% MeCN:0.03% HCl in water). Dilute product containing fractions with ethyl acetate then wash with 1 N NaOH followed by aqueous saturated sodium chloride. Dry the organics over MgSO4 then filter and concentrate to give the freebase (0.33 g off-white solid, 56%). MS (ES), m/z 521.1 (M+1).

Workup

  1. customQuench with water
  2. additionthen dilute with ethyl acetate
  3. filtrationDry organics over MgSO4 then filter
  4. concentrationconcentrate
  5. customPurify by reverse phase (5% MeCN:0.03% HCl in water→65% MeCN:0.03% HCl in water)
  6. additionDilute product containing fractions with ethyl acetate
  7. washthen wash with 1 N NaOH
  8. dry with materialDry the organics over MgSO4
  9. filtrationthen filter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-92a8cfd036b5410fbddd93eed407265f
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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