2-Fluoroethyl bromide → HCID 86651809, compound

HRID 529121Notes

Reaction equation

HRID 529121 reaction equation
CCN(C(C)C)C(C)C.Br[CH2:11][CH2:12][F:13].[NH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]2[N:22]([C:37]3[C:38]4[C@H:45]([CH3:46])[CH2:44][CH2:43][C:39]=4[N:40]=[CH:41][N:42]=3)[CH2:23][C:24]3([CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)[C:17]=12>CN(C=O)C>[F:13][CH2:12][CH2:11][NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]2[N:22]([C:37]3[C:38]4[C@H:45]([CH3:46])[CH2:44][CH2:43][C:39]=4[N:40]=[CH:41][N:42]=3)[CH2:23][C:24]3([CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:34])([CH3:35])[CH3:36])=[O:31])[CH2:26][CH2:25]3)[C:17]=12

Participants

5

Reactant 3

HCID 129822-Fluoroethyl bromideHCID 81531DiisopropylethylamineHCID 69810509HCID 69810509, compound

Product 1

HCID 86651809HCID 86651809, compoundYield 39.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

DIEA (0.015 mL, 0.093 mmol) and 1-bromo-2-fluoroethane (0.0067 mL, 0.075 mmol) was added to a stirred solution of (R)-tert-butyl 4-(aminomethyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (28 mg, 0.062 mmol) in DMF (0.6 mL). The reaction mixture was stirred at 80° C. overnight. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 60:1) to give (R)-tert-butyl 4-((2-fluoroethylamino)methyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (12 mg, 39%) as an oil. LCMS (APCI+) m/z 496 [M+H]+; Rt=3.03 min.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between EtOAc and water
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (DCM:MeOH, 60:1)

Sources & evidence

ORD record
ord-5b8b9a2fc06b4c759574dbbce21253ff
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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