Hydrochloric Acid → HCID 136341348, compound

HRID 579365Notes

Reaction equation

HRID 579365 reaction equation
Cl.[F:2][C:3]1[C:8](F)=[C:7]([C:10]2[CH:11]=[N:12][NH:13][CH:14]=2)[CH:6]=[CH:5][C:4]=1[C:15]1[S:19][C:18]([N:20]2[CH2:23][C:22]3([CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]3)[CH2:21]2)=[N:17][N:16]=1.[OH2:36]>O1CCOCC1.CO.CS(C)=O>[CH2:21]1[C:22]2([CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:23][N:20]1[C:18]1[S:19][C:15]([C:4]2[C:3]([F:2])=[CH:8][C:7]([C:10]3[CH:11]=[N:12][NH:13][CH:14]=3)=[CH:6][C:5]=2[OH:36])=[N:16][N:17]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 86727182HCID 86727182, compound

Product 1

HCID 136341348HCID 136341348, compoundYield 55%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent3×HCID 312751,4-DioxaneSolvent2×

Procedure

HCl (4M solution in dioxane, 545 μL, 2.179 mmol) was added to a stirred suspension of tert-butyl 2-(5-(2,3-difluoro-4-(1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (53 mg, 0.109 mmol) in dioxane (4 mL). The reaction mixture was stirred at room temperature for 2 hours then diluted with dioxane (2 mL), MeOH (5 mL), DMSO (5 mL) and a small amount of water, then loaded onto a 2 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (15 mL) then flushed with 10% DCM in [7M NH3 in MeOH] (20 mL). The DCM/MeOH/NH3 was removed in vacuo to afford the crude product as a brown solid. The crude material was heated in MeOH (5 mL) and the resulting suspension was cooled to room temperature then filtered under vacuum and rinsed with MeOH to afford the title compound as a pale brown solid (23 mg, 55% yield). LC-MS: Rt 0.68 min; MS m/z 387.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (s, 1H), 8.17 (s, 2H), 7.15-7.05 (m, 2H), 3.87 (s, 4H), 2.70 (t, J=5.1 Hz, 4H), 1.73 (t, J=5.3 Hz, 4H).

Workup

  1. washThe cartridge was washed with MeOH (15 mL)
  2. customthen flushed with 10% DCM in [7M NH3 in MeOH] (20 mL)
  3. customThe DCM/MeOH/NH3 was removed in vacuo
  4. customto afford the crude product as a brown solid
  5. temperaturethe resulting suspension was cooled to room temperature
  6. filtrationthen filtered under vacuum
  7. washrinsed with MeOH

Sources & evidence

ORD record
ord-2e2fa5f2b0494d978a205ed77464ef4f
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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