Acetyl chloride → HCID 86695249, compound

HRID 1504084Notes

Reaction equation

HRID 1504084 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[N:8]1([CH:14]2[CH2:19][CH2:18][CH:17]([O:20][C:21]3[C:22]4[C:23]5[CH2:24][NH:25][CH2:26][CH2:27][C:28]=5[S:29][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:16][CH2:15]2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.C(Cl)(=O)C>C(Cl)Cl>[N:8]1([CH:14]2[CH2:15][CH2:16][CH:17]([O:20][C:21]3[C:22]4[C:23]5[CH2:24][N:25]([C:3](=[O:5])[CH3:2])[CH2:26][CH2:27][C:28]=5[S:29][C:30]=4[N:31]=[CH:32][N:33]=3)[CH2:18][CH2:19]2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86695247HCID 86695247, compound

Product 1

HCID 86695249HCID 86695249, compoundYield 25.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-[[4-(morpholin-4-yl)cyclohexyl]oxy]-8-thia-4,6,12-triazatricyclo[7.4.0.0[2,7]]trideca-1(9),2 (7),3,5-tetraene trifluoroacetate (100 mg, crude) in DCM (20 mL) was added TEA (108 mg, 1.07 mmol). The solution was stirred for 10 min at 0° C. under nitrogen. Then acetyl chloride (41.9 mg, 0.53 mmol) was added to the reaction solution at this temperature and the resulting solution was stirred for 1.5 h at room temperature. The reaction was then quenched by the addition of ethanol and concentrated under vacuum. 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. After concentration in vacuo and lyophilization overnight, the corresponding 1-(3-[[4-(morpholin-4-yl)cyclohexyl]oxy]-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 (22.1 mg) was obtained as a white solid. MS (ES): m/z 417 (M+H)+ and 429 (M+Na)+. 1H NMR (300 MHz, CD3OD): δ 8.54 (1H, s), 5.33-5.23 (1H, m), 4.91 (2H, s), 3.97, 3.90 (2H, t, t), 3.76-3.69 (4H, m), 3.05, 2.95 (2H, t, t), 2.67-2.58 (4H, t), 2.34-2.25 (3H, m), 2.25, 2.23 (3H, s, s), 2.10 (2H, d), 1.74-1.45 (4H, m).

Workup

  1. stirringthe resulting solution was stirred for 1.5 h at room temperature
  2. customThe reaction was then quenched by the addition of ethanol
  3. concentrationconcentrated under vacuum
  4. customThe crude product was purified by preparative HPLC under the following conditions (Waters)
  5. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min
  6. waitup to 95% in 1.5 min
  7. waitdown to 10% in 1.5 min)
  8. concentrationAfter concentration in vacuo and lyophilization overnight

Sources & evidence

ORD record
ord-2aacae6fb3b94b7785665ebf77dde11c
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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