Potassium Carbonate → HCID 57521143, compound

HRID 2369427Notes

Reaction equation

HRID 2369427 reaction equation
[CH3:1][NH:2][CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[CH2:19][CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:29][C:30]([N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31]>CN(C=O)C>[CH3:1][N:2]([CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[CH2:19][CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:5][CH2:4]1)[CH2:29][C:30]([N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1)=[O:31]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 884401-(Chloroacetyl)pyrrolidineHCID 575202421-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]cyclohexane-1,4-diamine

Product 1

HCID 57521143HCID 57521143, compoundYield 29.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-N-methyl-4-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]cyclohexane-1,4-diamine (200 mg, 0.33 mmol, 1.00 equiv, 50%) in DMF (5 mL) was added potassium carbonate (91.1 mg, 0.66 mmol, 2.00 equiv) and 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (73.5 mg, 0.50 mmol, 1.50 equiv) at room temperature under nitrogen. The resulting solution was stirred overnight at ambient temperature. The solids were filtered out and the filtrate was concentrated under vacuum. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH3HCO3 and CH3CN (5.0% CH3CN up to 50.0% in 11 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The fractions containing product were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired 2-[methyl[4-([7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]amino)cyclohexyl]amino]-1-(pyrrolidin-1-yl)ethan-1-one (40 mg) as a white solid. MS (ES, m/z): 414 (M+H+). 1H NMR (400 MHz, DMSO-d6): δ 8.25 (s, 1H), 5.97 (d, 1H), 4.02-4.04 (m, 1H), 3.49 (t, 2H), 3.35 (t, 2H), 3.21 (s, 2H), 3.09 (t, 2H), 2.95 (t, 2H), 2.39-2.51 (m, 3H), 2.25 (s, 3H), 1.95-2.03 (m, 2H), 1.69-1.88 (m, 6H), 1.33-1.51 (m, 4H).

Workup

  1. filtrationThe solids were filtered out
  2. concentrationthe filtrate was concentrated under vacuum
  3. customThe crude product (150 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  4. waitmobile phase, water with 0.05% NH3HCO3 and CH3CN (5.0% CH3CN up to 50.0% in 11 min)
  5. additionThe fractions containing product
  6. customwere collected
  7. custompartially evaporated
  8. customto remove water and CH3CN under reduced pressure
  9. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-a1050b23fcbf4c3aa37a4b9122868963
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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