Dichloromethane → HCID 86664041, compound

HRID 712331Notes

Reaction equation

HRID 712331 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[O:12][CH2:13][C:14]#[C:15][C:16]1[C:24]2[S:23][C:22]([N:25]3CN(C)C[N:27]([CH2:32][CH3:33])[C:26]3=[O:34])=[N:21][C:20]=2[CH:19]=[C:18]([C:35]2[CH:36]=[N:37][C:38]([N:41]3[CH2:46][CH2:45][C:44]([CH2:52][CH3:53])([C:47]([O:49]CC)=[O:48])[CH2:43][CH2:42]3)=[N:39][CH:40]=2)[CH:17]=1.[OH-].[Na+].C(Cl)Cl>CCO.O.CO>[O:12]1[CH2:13][CH2:14][C:15]([C:16]2[C:24]3[S:23][C:22]([NH:25][C:26](=[O:34])[NH:27][CH2:32][CH3:33])=[N:21][C:20]=3[CH:19]=[C:18]([C:35]3[CH:40]=[N:39][C:38]([N:41]4[CH2:42][CH2:43][C:44]([CH2:52][CH3:53])([C:47]([OH:49])=[O:48])[CH2:45][CH2:46]4)=[N:37][CH:36]=3)[CH:17]=2)=[N:3]1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 66977300HCID 66977300, compound

Product 1

HCID 86664041HCID 86664041, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Ethyl 1-[5-[7-[3-(1,3-dioxoisoindolin-2-yl)oxyprop-1-ynyl]-2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (233 mg, 0.32 mmol) was suspended in EtOH (20 mL) and sodium hydroxide solution (10 mL, 1 M, aq) was added to give a light yellow solution. The solution was heated at 100° C. then cooled to rt after 48 h. The mixture was concentrated to dryness under reduced pressure and remaining water azeotroped with MeCN. The resulting yellow residue was suspended in MeOH with sonication and warming then filtered through a PTFE filter cup. A white (salt-like) solid was obtained (discarded) and a yellow filtrate. The yellow filtrate was concentrated to dryness under reduced pressure to give a yellow solid which was suspended in water, sonicated, DCM added and the mixture filtered through a PTFE filter cup leaving a pale yellow solid. This solid was dissolved in MeOH, passed through the filter cup and the solution concentrated to dryness under reduced pressure to give a pale yellow solid which was purified by chromatography, Biotage SP4, 40 g Si cartridge, 0-5% MeOH in DCM. The relevant fractions were combined to afford Compound 197 as a pale yellow solid, 9 mg. 1H NMR (MeOD): δ 8.67 (2H, s), 7.85 (1H, d, J=1.6 Hz), 7.51 (1H, d, J=1.6 Hz), 4.57 (2H, t, J=10.2 Hz), 4.57 (2H, m), 3.60 (2H, t, J=10.2 Hz), 3.36 (2H, q, J=7.2 Hz), 3.24 (2H, m), 2.22 (2H, dm, J=13.4 Hz), 1.64 (2H, J=7.5 Hz), 1.45 (2H, m), 1.24 (3H, t, J=7.2 Hz), 0.93 (3H, t, J=7.5 Hz). MS: 524.14 [M+H]+.

Workup

  1. customto give a light yellow solution
  2. temperaturethen cooled to rt after 48 h
  3. concentrationThe mixture was concentrated to dryness under reduced pressure
  4. customazeotroped with MeCN
  5. customThe resulting yellow residue was suspended in MeOH with sonication
  6. temperaturewarming
  7. filtrationthen filtered through a PTFE
  8. filtrationfilter
  9. customA white (salt-like) solid was obtained (discarded)
  10. concentrationThe yellow filtrate was concentrated to dryness under reduced pressure
  11. customto give a yellow solid which
  12. customsonicated
  13. filtrationthe mixture filtered through a PTFE
  14. filtrationfilter
  15. customcup leaving a pale yellow solid
  16. concentrationthe solution concentrated to dryness under reduced pressure
  17. customto give a pale yellow solid which
  18. customwas purified by chromatography, Biotage SP4, 40 g Si cartridge, 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-2fe16fe7699d4585a92a54aa754ef542
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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