HCID 86695253, compound → HCID 86695252, compound

HRID 1504088Notes

Reaction equation

HRID 1504088 reaction equation
Cl[C:2]1[C:3]2[C:4]3[CH2:5][N:6]([C:15](=[O:17])[CH3:16])[CH2:7][CH2:8][C:9]=3[S:10][C:11]=2[N:12]=[CH:13][N:14]=1.Cl.Cl.[N:20]1([C@H:26]2[CH2:31][CH2:30][C@H:29]([NH2:32])[CH2:28][CH2:27]2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CN(C)C=O>[N:20]1([CH:26]2[CH2:27][CH2:28][CH:29]([NH:32][C:2]3[C:3]4[C:4]5[CH2:5][N:6]([C:15](=[O:17])[CH3:16])[CH2:7][CH2:8][C:9]=5[S:10][C:11]=4[N:12]=[CH:13][N:14]=3)[CH2:30][CH2:31]2)[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1

Participants

4

Reactant 2

HCID 86695253HCID 86695253, compoundHCID 178478723HCID 178478723, compound

Product 1

HCID 86695252HCID 86695252, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-[3-chloro-8-thia-4,6,12-triazatricyclo[7.4.0.0-[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl]ethan-1-one (100 mg, 0.37 mmol, 1.00 equiv) and trans-4-(morpholin-4-yl)cyclohexan-1-amine dihydrochloride (412 mg, 1.61 mol, 4.32 equiv) in 10 mL of N,N-dimethylformamide was added TEA (200 mg, 1.98 mmol, 5.29 equiv) and the resulting solution was stirred for 12 h at 50° C. under nitrogen. After concentration in vacuo, the crude product was purified by preparative HPLC under the following conditions (Waters): Column: Xbridge Prep C18, 5 μm, 19*50 mm; mobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min, up to 95% in 1.5 min, down to 10% in 1.5 min); detector: UV 254/220 nm. The product-containing fractions were collected and partially evaporated under reduced pressure and lyophilized overnight to give 76.9 mg (50%) of 1-(3-[[4-(morpholin-4-yl)cyclohexyl]amino]-8-thia-4,6,12-triazatricyclo[7.4.0.0-[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl)ethan-1-one as a white solid. MS (ES): m/z 416 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 1.40-1.60 (m, 4H), 2.08 (d, 2H), 2.20-2.45 (m, 6H), 2.60-2.70 (m, 4H), 2.92, 3.02 (t, t, 2H), 3.70-3.80 (m, 4H), 3.89, 3.95 (t, t, 2H), 4.05-4.22 (m, 1H), 4.96, 5.00 (s, s, 2H), 8.29, 8.30 (s, s, 1H).

Workup

  1. concentrationAfter concentration in vacuo
  2. customthe crude product was purified by preparative HPLC under the following conditions (Waters)
  3. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min
  4. waitup to 95% in 1.5 min
  5. waitdown to 10% in 1.5 min)
  6. customThe product-containing fractions were collected
  7. custompartially evaporated under reduced pressure
  8. waitlyophilized overnight

Sources & evidence

ORD record
ord-5358f02986e544e486e6ce0b73ab713d
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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