Oxolane--water (1/1) → HCID 74766597, compound

HRID 2199779Notes

Reaction equation

HRID 2199779 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[S:15][C:16]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[C:17]([C:19]#[N:20])[N:18]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[O:29]1CCCC1.O>O>[C:1]([O:5][C:6](=[O:28])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]2[S:15][C:16]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)=[C:17]([C:19](=[O:29])[NH2:20])[N:18]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 21881883Oxolane--water (1/1)HCID 118556216HCID 118556216, compound

Product 1

HCID 74766597HCID 74766597, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A solution of {(R)-1-[4-cyano-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester (455 mg, 1.14 mmol) in 10:1 v/v tetrahydrofuran/water (16.5 mL total volume) was degassed by bubbling in argon for 10 minutes with stiffing. Hydrido-(dimethylphosphinous acid-kP)[hydrogen bis(dimethylphosphnito-kP]platinum (II) (CAS number 173416-05-2) (78 mg, 183 μmol) was added and the mixture was heated to 150° C. by microwave for 45 minutes. The reaction mixture was cooled to ambient temperature, poured into water (150 mL) and extracted with 1:1 v/v tetrahydrofuran/ethyl acetate (4×50 mL), the combined organic extracts were washed with brine (2×40 mL), dried over sodium sulfate, filtered and concentrated in vacuo to a yellow solid. The crude product was purified by chromatography using silica gel gradient eluted from 30% up to 70% v/v ethyl acetate in hexanes. The product containing fractions were combined and concentrated in vacuo to obtain {(R)-1-[4-carbamoyl-5-(pyridin-2-ylamino)-thiazol-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester as an off white solid (362 mg, 76%). LC/MS: m/z calculated for C19H26N6O3S ([M−H]−): 417.5. Found: 417.4 (negative mode electrospray ionization).

Workup

  1. customby bubbling in argon for 10 minutes
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. extractionextracted with 1:1 v/v tetrahydrofuran/ethyl acetate (4×50 mL)
  4. washthe combined organic extracts were washed with brine (2×40 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo to a yellow solid
  8. customThe crude product was purified by chromatography
  9. washeluted from 30% up to 70% v/v ethyl acetate in hexanes
  10. additionThe product containing fractions
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f8ccda2ffb18469899c33aa205789143
Source dataset
uspto-grants-2016_06
Patent number
US09359345B2

Reaction notes

Loading…