5-Cyanopyridine-2-carboxylic acid → HCID 90308633, compound

HRID 627741Notes

Reaction equation

HRID 627741 reaction equation
[NH2:1][C:2]1[CH:30]=[N:29][C:5]2[O:6][CH2:7][CH2:8][C@@H:9]3[C@@:14]([CH3:15])([C:4]=2[CH:3]=1)[N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:11]1([CH2:26][CH2:25][CH2:24]1)[S:10]3(=[O:28])=[O:27].[C:31]([C:33]1[CH:34]=[CH:35][C:36]([C:39](O)=[O:40])=[N:37][CH:38]=1)#[N:32].O.[Cl-].C[NH+]1CCOCC1>C1COCC1.CO>[C:31]([C:33]1[CH:34]=[CH:35][C:36]([C:39]([NH:1][C:2]2[CH:30]=[N:29][C:5]3[O:6][CH2:7][CH2:8][C@@H:9]4[C@@:14]([CH3:15])([C:4]=3[CH:3]=2)[N:13]=[C:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:20])[CH3:21])[C:11]2([CH2:26][CH2:25][CH2:24]2)[S:10]4(=[O:27])=[O:28])=[O:40])=[N:37][CH:38]=1)#[N:32]

Participants

5

Reactant 3

HCID 124007345-Cyanopyridine-2-carboxylic acidHCID 69640569HCID 69640569, compoundHCID 90307375HCID 90307375, compound

Product 1

HCID 90308633HCID 90308633, compound

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of tert-butyl ((4a′R,11b′R)-10′-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]-2′-yl)carbamate (0.086 g, 0.197 mmol) in THF/MeOH (3/0.9 mL) was added 5-cyano-2-pyridinecarboxylic acid (0.035 g, 0.236 mmol) and 4-(4,)dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate, 99+% (0.070 g, 0.236 mmol) and the resulting mixture was stirred at rt for 1.5 h. The reaction was quenched with sat. NaHCO3 and extracted with DCM. The combined organics were dried over Na2SO4, filtered, concentrated. The residue was purified by silica gel chromatography using a gradient 0-3% MeOH/DCM solvent system to afford a white solid as 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 as a white solid. MS m/z=588.9 (M+Na).

Workup

  1. customThe reaction was quenched with sat. NaHCO3
  2. extractionextracted with DCM
  3. dry with materialThe combined organics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bf0376bce27e49099e807dddcb63866d
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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