Hydrochloric Acid → HCID 44135981, compound

HRID 1500732Notes

Reaction equation

HRID 1500732 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][NH:9][C:10]([C:12]2[N:13]=[CH:14][C:15]3[N:16]([CH:27]=[N:28][CH:29]=3)[C:17]=2[NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[O:11])[CH2:4][O:3]1.Cl.O1CCOCC1.S([O-])([O-])(=O)=O.[Na+].[Na+]>CO>[OH:6][C@H:5]([CH2:4][OH:3])[CH2:7][O:8][NH:9][C:10]([C:12]1[N:13]=[CH:14][C:15]2[N:16]([CH:27]=[N:28][CH:29]=2)[C:17]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26])=[O:11]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24436Sodium SulfateHCID 312751,4-DioxaneHCID 59140151HCID 59140151, compound

Product 1

HCID 44135981HCID 44135981, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a heterogeneous mixture of (R)—N-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-5-(2-fluoro-4-iodophenylamino)imidazo[1,5-a]pyrazine-6-carboxamide (69.5 mg, 0.13 mmol) in anhydrous methanol (1.6 mL) was added 4M HCl in 1,4-dioxane (0.13 mL, 0.5 mmol, 4.0 eq). The reaction mixture was stirred at room temperature for 10 minutes. Solid sodium sulfate (200 mg) was then added. The reaction mixture was absorbed onto silica and then subjected to flash chromatography (Si-PPC, gradient 0% to 40% methanol in dichloromethane) to give the title compound as yellow foam (43.2 mg, 67.3%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 11.90 (s, 1H), 10.30 (s, 1H), 8.82 (s, 1H), 7.95 (s, 1H), 7.91 (s, 1H), 7.74 (d, J=9.6 Hz, 1H), 7.44 (d, 8.4 Hz, 1H), 6.60 (t, J=8.4 Hz, 1H), 4.86 (d, J=4.4 Hz, 1H), 4.55 (broad s, 1H), 3.99-3.91 (m, 1H), 3.79-3.69 (m, 2H), 3.39 (broad s, 2H); LCMS (method E2): RT=8.40 min, [M+H]+=488.

Workup

  1. customThe reaction mixture was absorbed onto silica

Sources & evidence

ORD record
ord-1d0dfaca446e483e9237104a294ec9c9
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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