Potassium Carbonate → N,N-dimethyl-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]acetamide

HRID 2369430Notes

Reaction equation

HRID 2369430 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.Cl[CH2:23][C:24]([N:26]([CH3:28])[CH3:27])=[O:25].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:27][N:26]([CH3:28])[C:24](=[O:25])[CH2:23][N:2]([CH3:1])[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

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 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 57521244N,N-dimethyl-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]acetamideYield 27.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Note: For the preparation of the starting material compound 1, see Example 147. 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 (90 mg, 0.30 mmol, 1.00 equiv) in DMF (10 mL) was added 2-chloro-N,N-dimethylacetamide (54.45 mg, 0.45 mmol, 1.50 equiv) and potassium carbonate (83 mg, 0.60 mmol, 2.00 equiv) at room temperature under nitrogen. The resulting solution was stirred overnight at ambient temperature. After completion of the reaction, the solids were removed by filtration and the filtrate was concentrated under vacuum. The crude product (120 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% NH4HCO3 and CH3CN (5.0% CH3CN up to 49.0% in 13 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 N,N-dimethyl-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]acetamide (31.8 mg) as a white solid. MS (ES, m/z): 388 (M+H+). 1H NMR (400 MHz, DMSO): δ 8.25 (s, 1H), 5.98 (d, 1H), 4.01-4.04 (m, 1H), 3.22 (s, 2H), 3.08 (t, 2H), 3.03 (s, 3H), 2.93 (t, 2H), 2.80 (s, 3H), 2.42-2.44 (m, 3H), 2.20 (s, 3H), 1.97-2.00 (m, 2H), 1.78-1.81 (m, 2H), 1.24-1.48 (m, 4H).

Workup

  1. customAfter completion of the reaction
  2. customthe solids were removed by filtration
  3. concentrationthe filtrate was concentrated under vacuum
  4. customThe crude product (120 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  5. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (5.0% CH3CN up to 49.0% in 13 min)
  6. customThe product-containing fractions were collected
  7. custompartially evaporated
  8. customto remove water and CH3CN under reduced pressure
  9. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-c86ff98247d7422c83559018058f6a91
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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