Hydrochloric Acid → HCID 86727183, compound

HRID 579359Notes

Reaction equation

HRID 579359 reaction equation
Cl.[F:2][C:3]1[C:8]([F:9])=[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.C(Cl)[Cl:37].O>O1CCOCC1.CO.CS(C)=O>[ClH:37].[F:2][C:3]1[C:8]([F:9])=[C:7]([C:10]2[CH:14]=[N:13][NH:12][CH:11]=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][NH:26][CH2:25][CH2:24]3)[CH2:21]2)=[N:17][N:16]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 6344DichloromethaneHCID 86727182HCID 86727182, compound

Product 1

HCID 86727183HCID 86727183, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

HCl (4M solution in dioxane, 113 μL, 0.45 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 (11 mg, 0.023 mmol) in dioxane (1 mL). The reaction mixture was stirred at room temperature for 18 hours then diluted with a roughly 1:1 mixture of MeOH:DCM (10 mL) and a drop of water was added. The resulting suspension was solubilized by addition of DMSO (5 mL) and the solution was loaded onto a 0.5 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (10 mL) then flushed with 10% DCM in [7M NH3 in MeOH] (10 mL). The DCM/MeOH/NH3 was removed in vacuo to afford the title compound as an off-white solid (7.4 mg, 85% yield). LC-MS: Rt 0.66 min; MS m/z 389.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 8.18 (s, 2H), 7.84 (ddd, J=8.6, 6.8, 1.7 Hz, 1H), 7.70 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 3.87 (s, 4H), 2.65 (t, J=5.0 Hz, 4H), 1.70 (t, J=5.4 Hz, 4H).

Workup

  1. washThe cartridge was washed with MeOH (10 mL)
  2. customthen flushed with 10% DCM in [7M NH3 in MeOH] (10 mL)
  3. customThe DCM/MeOH/NH3 was removed in vacuo

Sources & evidence

ORD record
ord-1b3afa1dae7045ff8083ab755efa333e
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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