Potassium Carbonate → HCID 71667677, compound

HRID 1503936Notes

Reaction equation

HRID 1503936 reaction equation
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C:23]([NH2:25])=[O:24])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1.Cl[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)=[O:29].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][N:2]([CH2:27][C:28](=[O:29])[N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1)[CH:3]1[CH2:8][CH2:7][CH:6]([O:9][C:10]2[C:21]3[C:20]4[C@@H:19]([CH2:22][C:23]([NH2:25])=[O:24])[CH2:18][CH2:17][C:16]=4[S:15][C:14]=3[N:13]=[CH:12][N:11]=2)[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 884401-(Chloroacetyl)pyrrolidineHCID 68110005HCID 68110005, compound

Product 1

HCID 71667677HCID 71667677, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide (90 mg, 0.25 mmol, 1.00 equiv) in 8 mL of DMF was added 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (55 mg, 0.37 mmol, 1.50 equiv) and potassium carbonate (69 mg, 0.50 mmol, 2.00 equiv) and the resulting solution was stirred overnight at room temperature. The reaction was quenched with water and extracted with DCM. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (80 mg) was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 16 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired 2-[(3R)-12-[(4-[methyl[2-oxo-2-(pyrrolidin-1-yl)ethyl]amino]cyclohexyl)oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]acetamide (50 mg) as a white solid. LCMS (ES): m/z 472 [M+H]+. 1H NMR (300 MHz, CD3OD): δ 8.43 (1H, s), 5.25-5.20 (1H, m), 3.85-3.69 (1H, m), 3.52 (2H, t), 3.42 (2H, t), 3.37 (2H, s), 3.15-2.85 (2H, m), 2.73-2.58 (2H, m), 2.29-2.18 (7H, m), 1.96-1.79 (6H, m), 1.67-1.47 (4H, m).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (80 mg) was purified by preparative HPLC under the following conditions (SHIMADZU)
  7. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 16 min)
  8. customThe product-containing fractions were collected
  9. custompartially evaporated
  10. customto remove water and CH3CN under reduced pressure
  11. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-bd8ce5eb60c54abab06b286931ea5964
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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