Pyridine → tert-butyl 4-(2-(4-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

HRID 1400919Notes

Reaction equation

HRID 1400919 reaction equation
[NH2:1][C:2]1[CH:37]=[CH:36][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[N:17]=[CH:18][N:19]([CH2:21][CH2:22][N:23]5[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]5)[CH:20]=4)[S:15][C:8]=23)=[C:4]([F:38])[CH:3]=1.[N:39]1[CH:44]=[CH:43][CH:42]=C[CH:40]=1.ClC(OC1C=CC=CC=1)=[O:47].C1(N)CC1>CN(C=O)C>[CH:44]1([NH:39][C:40](=[O:47])[NH:1][C:2]2[CH:37]=[CH:36][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]4[CH:13]=[C:14]([C:16]5[N:17]=[CH:18][N:19]([CH2:21][CH2:22][N:23]6[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:27][CH2:28]6)[CH:20]=5)[S:15][C:8]=34)=[C:4]([F:38])[CH:3]=2)[CH2:42][CH2:43]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 67442156tert-butyl 4-(2-(4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylate

Product 1

HCID 67440535tert-butyl 4-(2-(4-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1H-imidazol-1-yl)ethyl)piperazine-1-carboxylateYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 306 (2.10 g, 3.90 mmol) and pyridine (631 μl, 4.68 mmol) in DMF (20 ml) at 0° C. was added phenyl chloroformate (587 μl, 4.68 mmol). After 45 min cyclopropylamine (687 μl, 9.75 mmol) was added at 0° C. and the reaction mixture was heated at 60° C. for 30 min. After cooling to RT the reaction mixture was quenched by addition of water and extracted with AcOEt. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV), to afford the title compound 307 (1.4 g, 2.25 mmol, 58% yield) as a beige solid. MS (m/z): 622.33 (M+H).

Workup

  1. temperatureAfter cooling to RT the reaction mixture
  2. customwas quenched by addition of water
  3. extractionextracted with AcOEt
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 100 g cartridge; MeOH/DCM: 0/100 to 10/90 over 20 CV)

Sources & evidence

ORD record
ord-b4a138c52212437cb8cabe4df1eded2b
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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