Diisopropylamine → HCID 118092531, compound

HRID 2207388Notes

Reaction equation

HRID 2207388 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[NH:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[O:18].Br[CH2:20][C:21]1[N:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]([NH:34][C:35]3[N:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=3)[CH:30]=[C:31]([CH3:33])[CH:32]=2)=[CH:23][CH:22]=1>C1COCC1>[CH3:33][C:31]1[CH:32]=[C:27]([C:24]2[CH:23]=[CH:22][C:21]([CH2:20][N:13]3[CH2:17][CH2:16][CH2:15][C:14]3=[O:18])=[N:26][CH:25]=2)[CH:28]=[C:29]([NH:34][C:35]2[N:40]=[C:39]([C:41]([F:44])([F:42])[F:43])[CH:38]=[CH:37][N:36]=2)[CH:30]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 120252-PyrrolidoneHCID 131735900HCID 131735900, compoundHCID 178418339Butyllithium

Product 1

HCID 118092531HCID 118092531, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

n-BuLi (1.6 M, 303 μL, 0.484 mmol) was added to diisopropylamine (67.3 μL, 0.473 mmol) in THF (394 μL) at −78° C. The reaction was warmed to −40° C. and was stirred for 1 hour. The reaction mixture was cooled back to −78° C. and a solution of pyrrolidin-2-one (15.1 mg, 0.177 mmol) in THF (100 μL) was added dropwise. The reaction mixture was warmed to −40° C. and stirred for 1 hour. The reaction mixture was cooled back to −78° C. and a solution of N-{3-[6-(bromomethyl)pyridin-3-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (50.0 mg, 0.118 mmol) in THF (300 μL) was added. The reaction mixture was slowly warmed to room temperature and quenched with saturated aqueous ammonium chloride (1.00 mL) and THF was removed under reduced pressure. The reaction mixture was extracted with dichloromethane and the organic was dried over sodium sulfate and concentration under reduced pressure. The residue was purified by reverse phase prep HPLC (10-80% MeCN in water with 0.5% TFA) to yield 1-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}pyrrolidin-2-on. MS APCI calc'd for C22H21F3N5O [M+H]+ 428. found 428. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.82 (d, J=4.9 Hz, 1H), 8.78 (d, J=2.0, 1H), 8.04 (dd, J=2.3 Hz, 8.1 Hz, 1H), 7.95 (s, 1H), 7.56 (s, 1H), 7.38 (d, J=8.1, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.20 (s, 1H), 4.52 (s, 3H), 4.38 (br s, 2H), 3.37 (t, J=7.0 Hz, 2H), 2.31 (t, J=8.1 Hz, 2H), 1.96 (q, J=7.6 Hz, 15.1 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was cooled back to −78° C.
  2. temperatureThe reaction mixture was warmed to −40° C.
  3. stirringstirred for 1 hour
  4. temperatureThe reaction mixture was cooled back to −78° C.
  5. temperatureThe reaction mixture was slowly warmed to room temperature
  6. customquenched with saturated aqueous ammonium chloride (1.00 mL) and THF
  7. customwas removed under reduced pressure
  8. extractionThe reaction mixture was extracted with dichloromethane
  9. dry with materialthe organic was dried over sodium sulfate and concentration under reduced pressure
  10. customThe residue was purified by reverse phase prep HPLC (10-80% MeCN in water with 0.5% TFA)

Sources & evidence

ORD record
ord-f07096f3df02458f8c222587cc0b6239
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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