Acetic Acid → [6-(6-methoxy-3,4-dihydro-2H-1-oxa-4,5,9-triaza-phenanthren-3-yl)-pyridin-3-yl]-carbamic acid tert-butyl ester

HRID 1422926Notes

Reaction equation

HRID 1422926 reaction equation
C(O)(=O)C.[C:5]([O:9][C:10](=[O:35])[NH:11][C:12]1[CH:13]=[N:14][C:15]([C:18](=O)[CH2:19][O:20][C:21]2[CH:22]=[N:23][C:24]3[C:29]([C:30]=2[NH2:31])=[N:28][C:27]([O:32][CH3:33])=[CH:26][CH:25]=3)=[CH:16][CH:17]=1)([CH3:8])([CH3:7])[CH3:6].C([BH3-])#N.[Na+].ClCCl>CO>[C:5]([O:9][C:10](=[O:35])[NH:11][C:12]1[CH:13]=[N:14][C:15]([CH:18]2[NH:31][C:30]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([O:32][CH3:33])[N:28]=4)[N:23]=[CH:22][C:21]=3[O:20][CH2:19]2)=[CH:16][CH:17]=1)([CH3:8])([CH3:7])[CH3:6]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 67248964{6-[2-(4-Amino-6-methoxy-[1,5]naphthyridin-3-yloxy)-acetyl]-pyridin-3-yl}-carbamic acid tert-butyl ester

Product 1

HCID 67247039[6-(6-methoxy-3,4-dihydro-2H-1-oxa-4,5,9-triaza-phenanthren-3-yl)-pyridin-3-yl]-carbamic acid tert-butyl esterYield 49.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Acetic acid (110 mg, 1.83 mmol, 1.7 eq) is added at room temperature to a stirred solution of {6-[2-(4-amino-6-methoxy-[1,5]naphthyridin-3-yloxy)-acetyl]-pyridin-3-yl}-carbamic acid tert-butyl ester (470 mg, 1.10 mmol 1.0 eq) in methanol (20 mL) and the resulting mixture is stirred at room temperature for 1 hour before the addition of sodium cyanoborohydride (370 mg, 5.89 mmol, 5.3 eq). After 4 hours stirring at room temperature, the reaction mixture is extracted with dichloromethane (3×10 mL) and a saturated sodium hydrogen carbonate aqueous solution (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 200:1 to 50:1, v/v) to afford [6-(6-methoxy-3,4-dihydro-2H-1-oxa-4,5,9-triaza-phenanthren-3-yl)-pyridin-3-yl]-carbamic acid tert-butyl ester as a light yellow solid (222 mg, 49% yield).

Workup

  1. extractionthe reaction mixture is extracted with dichloromethane (3×10 mL)
  2. dry with materialThe combined organic layers are dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue that
  6. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-d4430c0bcce04fc5b137f254e658c3de
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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