Hydrochloric Acid → HCID 178458934, compound

HRID 2272667Notes

Reaction equation

HRID 2272667 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[N:16]=[C:15]([C:17]4[S:21][C:20]([C:22]([C@H:26]5[CH2:31][CH2:30][C@H:29]([C:32]([O:34]C)=[O:33])[CH2:28][CH2:27]5)([OH:25])[CH2:23][CH3:24])=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:36])[CH:12]=3)[CH:5]=2)[CH2:3][CH2:2]1.[OH-].[K+].CO.Cl>O.C(O)(C)C.C(Cl)(Cl)Cl>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]3[N:16]=[C:15]([C:17]4[S:21][C:20]([C:22]([C@H:26]5[CH2:27][CH2:28][C@H:29]([C:32]([OH:34])=[O:33])[CH2:30][CH2:31]5)([OH:25])[CH2:23][CH3:24])=[N:19][CH:18]=4)[CH:14]=[C:13]([CH3:36])[CH:12]=3)[CH:5]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14797Potassium HydroxideHCID 178458935HCID 178458935, compound

Product 1

HCID 178458934HCID 178458934, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6212ChloroformSolvent

Conditions

Temperature
80 °C

Procedure

To a flask containing methyl trans-4-[1-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]-cyclohexanecarboxylate (198 mg, 0.391 mmol) and potassium hydroxide (88 mg, 1.563 mmol) was added methanol (1 mL) and water (1 mL). The reaction vessel was sealed and heated to 80° C. for a period of 14 hours. After cooling the reaction, aqueous hydrochloric acid (1.0 M, 1.56 mL, 1.56 mmol) was added. The cloudy solution was diluted with additional water (10 mL) and stirring was continued for one hour. Chloroform and isopropanol (4:1; 20 mL total) were added and the biphasic mixture was transferred to a separatory funnel. The organic phase was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to yield trans-4-[1-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxylic acid. MS ESI calc'd. for C27H33N4O3S [M+H]+ 493. found 493. 1H NMR (500 MHz, DMSO-d6) δ 11.60-10.74 (br s, 1H), 8.48 (s, 1H), 8.27 (s, 1H), 7.75-7.29 (m, 2H), 7.26 (m, 2H), 5.68-5.47 (m, 1H), 2.42 (s, 3H), 2.29-2.12 (m, 1H), 2.12-1.84 (m, 7H), 1.84-1.73 (m, 1H), 1.54-1.42 (m, 1H), 1.43-1.13 (m, 6H), 1.13-0.97 (m, 3H), 0.88 (t, J=7.3 Hz, 3H). rhSyk activity=+++.

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. additionwas added
  4. customthe biphasic mixture was transferred to a separatory funnel
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-614a6bd8c68f42b08dc75808a3493917
Source dataset
uspto-grants-2015_09
Patent number
US09120785B2

Reaction notes

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