3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(7-Fluoro-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

HRID 518977Notes

Reaction equation

HRID 518977 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[F:16])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:18])[C:7](=[O:17])[NH:8][N:9]=1.O=[C:20]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21]1.C([BH3-])#N.[Na+]>CO.CC(O)=O>[C:27]([O:26][C:24]([N:22]1[CH2:23][CH:20]([NH:1][C:2]2[CH:3]=[C:4]3[C:13](=[CH:14][C:15]=2[F:16])[O:12][CH2:11][C:10]2[N:5]3[CH:6]([CH3:18])[C:7](=[O:17])[NH:8][N:9]=2)[CH2:21]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]

Participants

6

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5003444Sodium cyanoborohydrideHCID 867273266-Amino-7-fluoro-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 867273273-(7-Fluoro-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl esterYield 71%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 6-amino-7-fluoro-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.100 g, 0.400 mmol) and tert-butyl 3-oxoazetidine-1-carboxylate (0.171 g, 0.999 mmol) in MeOH (10 mL) and HOAc (1 mL) was stirred at rt for 1 h. Sodium cyanoborohydride (0.176 g, 2.80 mmol) was added and the reaction mixture was stirred at rt for 3 h. The reaction mixture was concentrated in vacuo and the residue was purified by column on silica gel (eluting with 0-10% MeOH in DCM to give 3-(7-fluoro-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 (0.115 g, 71%) as a crude gum, which was used directly in the next step. LC/MS (Table 1, Method 3) Rt=1.374 min.; MS m/z: 428 [M+23]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by column on silica gel (
  3. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-d49abecf33164291995311d7215c8283
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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