Hydrochloric Acid → HCID 89691190, compound

HRID 1504091Notes

Reaction equation

HRID 1504091 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@@H:11]1[CH2:23][C:22]2[C:21]3[C:20]([O:24][CH:25]4[CH2:30][CH2:29][CH:28]([N:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]4)=[N:19][CH:18]=[N:17][C:16]=3[S:15][C:14]=2[CH2:13][CH2:12]1)(C(C)(C)C)(C)C.Cl.[CH3:35][OH:36]>>[CH:35]([O:8][CH2:9][CH2:10][C@@H:11]1[CH2:23][C:22]2[C:21]3[C:20]([O:24][CH:25]4[CH2:26][CH2:27][CH:28]([N:31]([CH3:33])[CH3:32])[CH2:29][CH2:30]4)=[N:19][CH:18]=[N:17][C:16]=3[S:15][C:14]=2[CH2:13][CH2:12]1)=[O:36]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 89691365HCID 89691365, compound

Product 1

HCID 89691190HCID 89691190, compoundYield 55%

Procedure

To a solution of 4-[[(12S)-12-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-3-yl]oxy]-N,N-dimethylcyclohexan-1-amine (110 mg, 0.22 mmol, 1.00 equiv) in methanol (5 mL) was added hydrochloric acid (12 M, 0.5 mL) at 0° C. The resulting solution was stirred for 1 h at room temperature. The solvent was removed in vacuo and the crude product (80 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 53.0% in 16 min); flow rate: 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated under reduced pressure to remove water and CH3CN. The residue was lyophilized overnight to give the 2-[(12S)-3-[[4-(dimethylamino)cyclohexyl]oxy]-8-thia-4,6-diazatricyclo[7.4.0.0[2,7]]trideca-1(9),2(7),3,5-tetraen-12-yl]ethan-1-ol formate (46 mg, 55%) as an off-white semi-solid. MS (ES): m/z 376 (M+H)+. 1H NMR (300 MHz, CDCl3): δ 8.49 (d, 2H), 5.22 (s, 1H), 3.82 (t, 2H), 3.16 (m, 2H), 2.88 (s, 2H), 2.66 (s, 6H), 2.48 (t, 3H), 2.19 (s, 2H), 2.05 (d, 2H), 1.70 (m, 7H).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe crude product (80 mg) was purified by preparative HPLC under the following conditions (SHIMADZU)
  3. waitmobile phase: water (with 0.1% HCOOH) and CH3CN (6.0% CH3CN up to 53.0% in 16 min)
  4. customThe product-containing fractions were collected
  5. custompartially evaporated under reduced pressure
  6. customto remove water and CH3CN
  7. waitThe residue was lyophilized overnight

Sources & evidence

ORD record
ord-251d37cb15d4489cb7a7e323159f5b9d
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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