Diisopropylethylamine → HCID 178511541, compound

HRID 1819410Notes

Reaction equation

HRID 1819410 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][C:21]([F:24])([F:23])[F:22])[N:3]=1.CC[N:27]([CH:31]([CH3:33])[CH3:32])C(C)C>CN(C=O)C.CCOC(C)=O>[NH2:27][C@H:31]1[CH2:32][CH2:8][C@H:7]([CH2:2][NH:3][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][C:21]([F:24])([F:23])[F:22])[N:3]=2)[CH2:6][CH2:33]1

Participants

5

Reactant 2

HCID 81531DiisopropylethylamineHCID 57885586(4-Chloro-5-trifluoromethyl-pyrimidin-2-yl)-(2-trifluoromethoxy-benzyl)-amine

Product 1

HCID 178511541HCID 178511541, compoundYield 109.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of the above (4-chloro-5-trifluoromethyl-pyrimidin-2-yl)-(2-trifluoromethoxy-benzyl)-amine (80 mg, 0.22 mmol) in DMF (2 mL) was added the Boc-protected cyclohexyl amine (74 mg, 0.33 mmol) followed by DIPEA (37 μL, 0.22 mmol). The reaction mixture was stirred at 70° C. for 3 h. When the reaction was complete, the reaction mixture was diluted with EtOAc and washed with water (×4). The organic phase was dried over anhydrous Na2SO4 and concentrated in vacuo. The resulting residue was purified by silica gel preparative TLC using 95:5 CH2Cl2:MeOH as an eluent. The resulting residue was then re-dissolved in CH2Cl2 (10 mL) and TFA (1 mL) was added. The reaction mixture was stirred at room temperature for 2 h and treated with saturated NaHCO3. The product was extracted with CH2Cl2 and dried over anhydrous Na2SO4. Silica gel preparative TLC using CH2Cl2:MeOH:NH4OH 10:1:0.2 as an eluent afforded 56 mg (56%) of the title compound as a white solid, m/z 462.4 [M−1]+.

Workup

  1. washwashed with water (×4)
  2. dry with materialThe organic phase was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by silica gel preparative TLC
  5. dissolutionThe resulting residue was then re-dissolved in CH2Cl2 (10 mL)
  6. additionTFA (1 mL) was added
  7. stirringThe reaction mixture was stirred at room temperature for 2 h
  8. additiontreated with saturated NaHCO3
  9. extractionThe product was extracted with CH2Cl2
  10. dry with materialdried over anhydrous Na2SO4

Sources & evidence

ORD record
ord-1f48ef7454204d52b1b21694af66d410
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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