Hydrochloric Acid → HCID 68110005, compound

HRID 1503935Notes

Reaction equation

HRID 1503935 reaction equation
[C:1]([CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:23][CH2:22][CH:21]([N:24](C)[C:25](=O)OC(C)(C)C)[CH2:20][CH2:19]4)[C:7]=3[C:6]1=2)(=[O:3])[NH2:2].Cl>ClCCl>[CH3:25][NH:24][CH:21]1[CH2:22][CH2:23][CH:18]([O:17][C:8]2[C:7]3[C:6]4[C@@H:5]([CH2:4][C:1]([NH2:2])=[O:3])[CH2:16][CH2:15][C:14]=4[S:13][C:12]=3[N:11]=[CH:10][N:9]=2)[CH2:19][CH2:20]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68115445HCID 68115445, compound

Product 1

HCID 68110005HCID 68110005, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Into a 50-mL round-bottom flask placed a solution of tert-butyl N-(4-[[(3R)-3-(carbamoylmethyl)-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, 0.37 mmol, 1.00 equiv) in dichloromethane (4 mL) was added hydrochloric acid (12 M, 0.5 mL) at 0° C. and the resulting solution was stirred for 4 hr at 25° C. The reaction was then quenched with saturated aqueous sodium bicarbonate, extracted with 3×50 mL of DCM. The organic layers were combined and concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5 um; mobile phase: water with 100 mM NH4HCO3 and CH3CN (6.0% CH3CN up to 60% in 20 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 2-[(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]acetamide (83 mg, 62%) as a white solid. MS (ES): m/z 361 [M+H]+. 1H NMR (300 MHz, CD3OD): δ 8.43 (1H, s), 5.28 (1H, m), 3.76 (1H, m), 3.00-3.28 (1H, m), 2.97-2.99 (2H, m), 2.66-2.73 (1H, m), 2.42-2.49 (1H, m), 2.36 (3H, s), 2.29-2.18 (4H, m), 2.00-2.03 (2H, m), 1.65-1.57 (2H-m), 1.26-1.35 (2H, m).

Workup

  1. customInto a 50-mL round-bottom flask placed
  2. customThe reaction was then quenched with saturated aqueous sodium bicarbonate
  3. extractionextracted with 3×50 mL of DCM
  4. concentrationconcentrated under vacuum
  5. customThe crude product (150 mg) was purified by preparative HPLC under the following conditions (SHIMADZU)
  6. waitmobile phase: water with 100 mM NH4HCO3 and CH3CN (6.0% CH3CN up to 60% in 20 min)
  7. customThe product-containing fractions were collected
  8. custompartially evaporated
  9. customto remove water and CH3CN under reduced pressure
  10. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-dcd470fe9aa64f3bbe05139e32ee706c
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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