Acetyl chloride → HCID 86695239, compound

HRID 1504078Notes

Reaction equation

HRID 1504078 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[CH3:8][N:9]([CH3:30])[CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]3[C:29]=2[C:28]2[CH2:27][NH:26][CH2:25][CH2:24][C:23]=2[S:22]3)[CH2:12][CH2:11]1.C(Cl)(=O)C>ClCCl>[CH3:8][N:9]([CH3:30])[CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]3[C:29]=2[C:28]2[CH2:27][N:26]([C:3](=[O:5])[CH3:2])[CH2:25][CH2:24][C:23]=2[S:22]3)[CH2:12][CH2:11]1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86695240HCID 86695240, compound

Product 1

HCID 86695239HCID 86695239, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N,N-dimethyl-4-[8-thia-4-azatricyclo[7,4,0,0-[2,7]]trideca-1(13),2(7),9,11-tetraen-13-yloxy]cyclohexan-1-amine trifluoroacetate (43 mg) and TEA (50 mg, 0.49 mmol, 3.80 equiv) in 10 mL of dichloromethane at 0° C. was added acetyl chloride (20 mg, 0.25 mmol, 1.96 equiv) at 0° C. The resulting solution was stirred for 2 hours at this temperature under nitrogen. The reaction was then quenched with CH3OH 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); flow rate: 20 mL/min; UV detection at 254/220 nm. This resulted in 12.6 mg (26%) of 1-(13-[[4-(dimethylamino)cyclohexyl]oxy]-8-thia-4-azatricyclo[7.4.0.0-[2,7]]trideca-1(13),2(7),9,11-tetraen-4-yl)ethan-1-one as a white solid. MS (ES): m/z 375 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 1.30-1.65 (m, 4H), 1.94 (d, 2H), 2.13 (s, 3H), 2.20-2.32 (m, 9H), 2.81, 2.91 (t, t, 2H, J=5.7 Hz), 3.77, 3.84 (t, t, 2H, J=5.7 Hz), 5.02-5.18 (m, 1H), 8.38, 8.39 (s, s, 1H).

Workup

  1. customThe reaction was then quenched with CH3OH
  2. concentrationconcentrated under vacuum
  3. customThe crude product was purified by preparative HPLC under the following conditions (Waters)
  4. waitmobile phase: water with 0.05% NH4HCO3 and CH3CN (10% CH3CN up to 35% in 11 min
  5. waitup to 95% in 1.5 min
  6. waitdown to 10% in 1.5 min)
  7. customThis resulted in 12.6 mg (26%) of 1-(13-[[4-(dimethylamino)cyclohexyl]oxy]-8-thia-4-azatricyclo[7.4.0.0-[2,7]]trideca-1(13),2(7),9,11-tetraen-4-yl)ethan-1-one as a white solid

Sources & evidence

ORD record
ord-60122e3553224eb0be4a9b33f1bc513a
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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