3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → HCID 86727314, compound

HRID 518965Notes

Reaction equation

HRID 518965 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[CH3:16])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:18])[C:7](=[O:17])[NH:8][N:9]=1.[C:19]([O:23][C:24]([N:26]1[CH2:29][C:28](=O)[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[C:19]([O:23][C:24]([N:26]1[CH2:29][CH:28]([NH:1][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[CH3:16])[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:18])[C:7](=[O:17])[NH:8][N:9]=2)[CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5003444Sodium cyanoborohydrideHCID 86727313HCID 86727313, compound

Product 1

HCID 86727314HCID 86727314, compoundYield 32.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 6-amino-4,7-dimethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (1.1 g, 4.5 mmol) and 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (1.53 g, 8.9 mmol) in methanol (45 mL) and acetic acid (5 mL) was stirred at rt for 2 h. Sodium cyanoborohydride (0.563 g, 8.9 mmol) was added and the resulting dark solution was stirred at rt for 14 h. The solvent was removed in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with 33% EtOAc in petroleum ether) to give 3-(4,7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (racemate, 0.580 g, 1.45 mmol, 32%) as an off-white powder. The racemate was further separated by chiral SFC (Table 2, Method 3) to give two enantiomers: 3-(4(R),7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (enantiomer 1, SFC (Table 1, Method 8), Rt=3.090 min, 0.250 g, 14%) and 3-(4(S),7-dimethyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (enantiomer 2, SFC (Table 1, Method 8), Rt=4.151 min, 0.240 g, 13%). LC/MS (Table 1, Method 2) Rt=1.065 min.; MS m/z: 424 [M+23]+.

Workup

  1. customThe solvent was removed in vacuo
  2. customto give the crude product, which
  3. customwas purified by column chromatography on silica gel (eluting with 33% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-6dcb1bd752ff45609fc9df6716ce9732
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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