3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → HCID 86727290, compound

HRID 518949Notes

Reaction equation

HRID 518949 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=1.[C:18]([O:22][C:23]([N:25]1[CH2:28][C:27](=O)[CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C([BH3-])#N.[Na+]>CO.CC(O)=O>[C:18]([O:22][C:23]([N:25]1[CH2:28][CH:27]([NH:1][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][CH:15]=2)[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:17])[C:7](=[O:16])[NH:8][N:9]=2)[CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5003444Sodium cyanoborohydrideHCID 867272916-Amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 86727290HCID 86727290, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 6-amino-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #2, Step E; 5 g, 21.6 mmol) and 3-oxo-azetidine-1-carboxylic acid tert-butyl ester (7.37 g, 43.1 mmol) in MeOH (90 mL) and HOAc (10 mL) was stirred at rt for 2 h. Sodium cyanoborohydride (2.7 g, 43.1 mmol) was added in portions and the resulting dark solution was stirred at rt for 2 h. The solvent was removed in vacuo and the residue was washed with aqueous Na2CO3 (100 mL) and extracted with EtOAc (4×100 mL). The combined organic phase was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10-50% EtOAc in petroleum ether) to give 3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (4.48 g, 54%) as a solid. 1H NMR (CDCl3, 400 MHz): δ 8.28 (brs, 1H), 6.87 (d, J=8.4 Hz, 1H), 6.15 (s, 1H), 6.13 (d, J=8.4 Hz, 1H), 4.70 (m, 1H), 4.58 (d, J=13.2 Hz, 2H), 4.30 (m, 2H), 4.17 (m, 1H), 4.01 (m, 1H), 3.75 (m, 2H), 1.51 (d, J=6.8 Hz, 3H), 1.47 (s, 9H).

Workup

  1. customThe solvent was removed in vacuo
  2. washthe residue was washed with aqueous Na2CO3 (100 mL)
  3. extractionextracted with EtOAc (4×100 mL)
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel (eluting with 10-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-24299e7ad3904713ba4fb71cb765e913
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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