Triethylamine → {1-[6-Fluoro-4-(2-{5-fluoro-2-[2-(2-oxo-2,3-dihydro-imidazol-1-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophen-7-yl)-pyridin-3-yl]-ethyl}-carbamic acid tert-butyl ester

HRID 561028Notes

Reaction equation

HRID 561028 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([F:33])=[CH:14][C:15]=1[C:16]1[C:21]2[S:22][C:23]([C:25]3[C:30]([F:31])=[CH:29][N:28]=[C:27](Cl)[N:26]=3)=[CH:24][C:20]=2[CH:19]=[CH:18][CH:17]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[NH2:35][CH2:36][CH2:37][N:38]1[CH:42]=[CH:41][NH:40][C:39]1=[O:43].C(N(CC)CC)C>CN1CCCC1=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:34])[NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([F:33])=[CH:14][C:15]=1[C:16]1[C:21]2[S:22][C:23]([C:25]3[C:30]([F:31])=[CH:29][N:28]=[C:27]([NH:35][CH2:36][CH2:37][N:38]4[CH:42]=[CH:41][NH:40][C:39]4=[O:43])[N:26]=3)=[CH:24][C:20]=2[CH:19]=[CH:18][CH:17]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 21843640HCID 21843640, compoundHCID 86640495(1-{4-[2-(2-Chloro-5-fluoro-pyrimidin-4-yl)-benzo[b]thiophen-7-yl]-6-fluoro-pyridin-3-yl}-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 66997925{1-[6-Fluoro-4-(2-{5-fluoro-2-[2-(2-oxo-2,3-dihydro-imidazol-1-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophen-7-yl)-pyridin-3-yl]-ethyl}-carbamic acid tert-butyl esterYield 74%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

Combine (1-{4-[2-(2-chloro-5-fluoro-pyrimidin-4-yl)-benzo[b]thiophen-7-yl]-6-fluoro-pyridin-3-yl}-ethyl)-carbamic acid tert-butyl ester (150 mg, 0.3 mmol), 1-(2-amino-ethyl)-1,3-dihydro-imidazol-2-one (70 mg, 0.55 mmol) and triethylamine (80 mg, 0.8 mmol) in N-methylpyrrolidone (1.0 mL) in a pressure tube. Heat the reaction mixture at 130° C. for 1 hour in a microwave reactor and then cool to room temperature. Dilute the reaction mixture with ethyl acetate, and wash with water and saturated aqueous sodium chloride. Separate the organic layer from the aqueous layer and dry over MgSO4. After filtration, evaporate the organic solvent to give the crude. Purify the crude by column chromatography (10% methanol in dichloromethane) to afford the desired product (80 mg, 74%). MS (ES) m/z 538 [M+t-Bu]+, 494 [M-Boc]−, 616 [M+Na]+.

Workup

  1. temperaturecool to room temperature
  2. washwash with water and saturated aqueous sodium chloride
  3. customSeparate the organic layer from the aqueous layer
  4. dry with materialdry over MgSO4
  5. filtrationAfter filtration
  6. customevaporate the organic solvent
  7. customto give the crude
  8. customPurify the crude by column chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-a4ac7988124a4502ba37531fa3a2c7d3
Source dataset
uspto-grants-2011_11
Patent number
US08063212B2

Reaction notes

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