Trifluoroacetic acid → HCID 90308634, compound

HRID 627742Notes

Reaction equation

HRID 627742 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]([NH:11][C:12]2[CH:40]=[N:39][C:15]3[O:16][CH2:17][CH2:18][C@@H:19]4[C@@:24]([CH3:25])([C:14]=3[CH:13]=2)[N:23]=[C:22]([NH:26]C(=O)OC(C)(C)C)[C:21]2([CH2:36][CH2:35][CH2:34]2)[S:20]4(=[O:38])=[O:37])=[O:10])=[N:7][CH:8]=1)#[N:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+].[OH-].[Na+]>O>[NH2:26][C:22]1[C:21]2([CH2:34][CH2:35][CH2:36]2)[S:20](=[O:37])(=[O:38])[C@@H:19]2[CH2:18][CH2:17][O:16][C:15]3[N:39]=[CH:40][C:12]([NH:11][C:9](=[O:10])[C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][N:7]=4)=[CH:13][C:14]=3[C@@:24]2([CH3:25])[N:23]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 90308633HCID 90308633, compound

Product 1

HCID 90308634HCID 90308634, compoundYield 32.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To tert-butyl ((4a′R,11b′R)-10′-(5-cyanopicolinamido)-11b′-methyl-4′,4′-dioxido-4a′,5′,6′,11b′-tetrahydrospiro[cyclobutane-1,3′-pyrido[3′,2′:6,7]oxepino[4,5-b][1,4]thiazin]-2′-yl)carbamate was added TFA (0.015 ml, 0.197 mmol) and the resulting solution was stirred at rt for 15 min. The reaction mixture was poured into water and the pH was brought to >10 using sat. NaHCO3 and 5 N NaOH, then extracted with DCM. The combined organics were dried over Na2SO4, filtered, concentrated and purified by silica gel chromatography using a gradient 0-3% MeOH/DCM solvent system to afford a white solid as N-((4a′R,11b′R)-2′-amino-11b′-methyl-4′,4′-dioxido-4a′,5′,6′,11b′-tetrahydrospiro[cyclobutane-1,3′-pyrido[3′,2′:6,7]oxepino[4,5-b][1,4]thiazin]-10′-yl)-5-cyanopicolinamide (0.030 g, 0.064 mmol, 32.6% yield). MS m/z=466.9 (M+H).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-99eb45f3c089469ab5c8d216fe1577c0
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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