Diisopropylethylamine → 5-{2-[3-(2-Fluoro-ethoxy)-phenyl]-imidazo[1,2-a]pyrimidin-7-ylcarbamoyl}-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1958358Notes

Reaction equation

HRID 1958358 reaction equation
[F:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[N:12]=[C:13]3[N:18]=[C:17]([NH2:19])[CH:16]=[CH:15][N:14]3[CH:20]=2)[CH:8]=[CH:9][CH:10]=1.[CH2:21]([O:23][C:24]([C:26]1[CH:27]=[N:28][N:29]([CH3:34])[C:30]=1[C:31](O)=[O:32])=[O:25])[CH3:22].CCN(C(C)C)C(C)C>CCOC(C)=O>[CH2:21]([O:23][C:24]([C:26]1[CH:27]=[N:28][N:29]([CH3:34])[C:30]=1[C:31](=[O:32])[NH:19][C:17]1[CH:16]=[CH:15][N:14]2[CH:20]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH2:3][CH2:2][F:1])[CH:6]=3)[N:12]=[C:13]2[N:18]=1)=[O:25])[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 252475674-(Ethoxycarbonyl)-1-methyl-1H-pyrazole-5-carboxylic acidHCID 58446794HCID 58446794, compound

Product 1

HCID 534684555-{2-[3-(2-Fluoro-ethoxy)-phenyl]-imidazo[1,2-a]pyrimidin-7-ylcarbamoyl}-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

2-(3-(2-Fluoroethoxy)phenyl)imidazo[1,2-a]pyrimidin-7-amine (1 eq.) was combined with EtOAc (7.50 ml) to give a light yellow suspension. 4-(Ethoxycarbonyl)-1-methyl-1H-pyrazole-5-carboxylic acid (1 eq.) and DIPEA (6 eq.) were added. The reaction mixture was cooled down to 0° C. and n-propylphosphonic acid anhydride, cyclic trimer (1.17 g, 1.1 ml, 1.84 mmol, 2.50 eq.) was added dropwise. After stirring at 0° C. during 30 min, the reaction mixture was stirred and allowed to warm-up to RT overnight. The reaction mixture (yellow solution) was poured into 50 ml EtOAc and extracted with H2O (1×30 ml). The aqueous layer was back-extracted with DCM (3×20 ml). The organic layers were combined and washed with sat. NaCl-solution (1×30 ml), dried over MgSO4, filtrated and concentrated under vacuum to give a yellow solid (207 mg). The crude material was purified by flash chromatography (silica gel, 20 g, CH2Cl2 to 50% CH2Cl2/MeOH/NH3 aq. 140:10:1). Yellow solid (332 mg, 31%).

Workup

  1. customto give a light yellow suspension
  2. stirringthe reaction mixture was stirred
  3. temperatureto warm-up to RT overnight
  4. extractionextracted with H2O (1×30 ml)
  5. extractionThe aqueous layer was back-extracted with DCM (3×20 ml)
  6. washwashed with sat. NaCl-solution (1×30 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltrated
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-5efa4172288a46e7a3c0988cf31e7838
Source dataset
uspto-grants-2013_04
Patent number
US08410117B2

Reaction notes

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