Potassium Carbonate → HCID 86345072, compound

HRID 1504096Notes

Reaction equation

HRID 1504096 reaction equation
Cl.[CH3:2][NH:3][CH:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[C:22]3[C:21]4[C@@H:20]([CH2:23][C@H:24]([OH:26])[CH3:25])[CH2:19][CH2:18][C:17]=4[S:16][C:15]=3[N:14]=[CH:13][N:12]=2)[CH2:6][CH2:5]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1)=[O:36]>CN(C=O)C>[OH:26][C@H:24]([CH3:25])[CH2:23][C@H:20]1[CH2:19][CH2:18][C:17]2[S:16][C:15]3[N:14]=[CH:13][N:12]=[C:11]([O:10][CH:7]4[CH2:6][CH2:5][CH:4]([N:3]([CH3:2])[CH2:34][C:35]([N:37]5[CH2:41][CH2:40][CH2:39][CH2:38]5)=[O:36])[CH2:9][CH2:8]4)[C:22]=3[C:21]1=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 884401-(Chloroacetyl)pyrrolidineHCID 86695257HCID 86695257, compound

Product 1

HCID 86345072HCID 86345072, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A 50-mL round-bottom flask was charged with a solution of tert-butyl N-(4-[[(3R)-3-[(2R)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (170 mg, 0.38 mmol, 1.0 equiv) in 5.5 mL of dichloromethane cooled to 0° C. Then hydrochloric acid (12 M, 0.5 mL) was added and the resulting solution was stirred for 3 h at room temperature. The reaction mixture was concentrated under reduced pressure to give (2R)-1-[(3R)-12-[[4-(methylamino)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-3-yl]propan-2-ol hydrochloride (130 mg, crude) as a light yellow oil. The resulting hydrochloride (130 mg, crude) was dissolved in DMF (5 mL). Potassium carbonate (359 mg) and 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (125 mg) were added at room temperature and the resulting mixture was stirred for 14 h at 25° C. After completion of the reaction, the product was extracted with DCM, washed with brine and concentrated in vacuo. The crude product (160 mg) was purified by preparative HPLC under the following conditions (SHIMADZU): Column: SunFire Prep C18, 19*150 mm, 5 μm; mobile phase: water (with 0.1% HCOOH) and CH3CN (6.0% CH3CN up to 50.0% in 25 min); UV detection at 254/220 nm. The product containing fractions were collected and evaporated to remove the water and CH3CN to give 2-[(4-[[(3R)-3-[(2R)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)(methyl)amino]-1-(pyrrolidin-1-yl)ethan-1-one (52.7 mg) as a white solid. MS (ES): m/z 473 (M+H)+. 1H NMR (400 MHz, CD3OD): δ 8.46 (1H, s), 5.32-5.18 (1H, m), 3.94-3.92 (1H, m), 3.57 (2H, t), 3.45 (2H, t), 3.36 (3H, m), 3.08-3.10 (1H, m), 2.96-2.98 (1H, m), 2.67-2.62 (2H, m), 2.41-2.29 (6H, m), 2.070-1.97 (5H, m), 1.95-1.87 (2H, m), 1.64-1.52 (5H, m), 1.30 (3H, d).

Workup

  1. customAfter completion of the reaction
  2. extractionthe product was extracted with DCM
  3. washwashed with brine
  4. concentrationconcentrated in vacuo
  5. customThe crude product (160 mg) was purified by preparative HPLC under the following conditions (SHIMADZU)
  6. waitmobile phase: water (with 0.1% HCOOH) and CH3CN (6.0% CH3CN up to 50.0% in 25 min)
  7. additionThe product containing fractions
  8. customwere collected
  9. customevaporated
  10. customto remove the water and CH3CN

Sources & evidence

ORD record
ord-e4c75e5da86449ccbff2d694bd6718a0
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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