3-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11 b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester → 3-((R)-8-ethyl-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

HRID 519144Notes

Reaction equation

HRID 519144 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:33])([N:12]2[C:28]3[C:15](=[CH:16][C:17]4[O:18][CH2:19][C:20]5[N:25]([C:26]=4[CH:27]=3)[C@H:24]([CH3:29])[C:23](=[O:30])[NH:22][N:21]=5)[C:14]([CH:31]=[CH2:32])=[CH:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([N:12]2[C:28]3[C:15](=[CH:16][C:17]4[O:18][CH2:19][C:20]5[N:25]([C:26]=4[CH:27]=3)[C@H:24]([CH3:29])[C:23](=[O:30])[NH:22][N:21]=5)[C:14]([CH2:31][CH3:32])=[CH:13]2)([CH3:33])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 867275353-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11 b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867275363-((R)-8-ethyl-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl esterYield 49.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 3-methyl-3-((R)-1-methyl-2-oxo-8-vinyl-1,2,3,5-tetrahydro-6-oxa-3,4,10,11 b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester (0.08 g, 0.177 mmol) and 10% Pd/C (0.002 g, 0.018 mmol) in methanol (2 mL) was stirred under an atmosphere of H2 at 20° C. for 2.5 h. The mixture was filtered and the filtrate was evaporated in vacuo. The residue was purified by prep-HPLC (Table 3, Method 32) to give 3-((R)-8-ethyl-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.04 g, 49%) as a gum. 1H NMR (400 MHz, methanol-d4): δ 7.18 (s, 1H), 7.00 (s, 1H), 6.81 (s, 1H), 4.98 (m, 1H), 4.61-4.47 (m, 4H), 4.27 (m, 2H), 2.70 (q, J=7.6 Hz, 2H), 1.77 (s, 3H), 1.50-1.47 (m, 12H), 1.32 (m, J=7.6 Hz, 3H). LC/MS (Table 1, Method 25) Rt=0.896 min.; MS m/z: 454 [M+H]+.

Workup

  1. filtrationThe mixture was filtered
  2. customthe filtrate was evaporated in vacuo
  3. customThe residue was purified by prep-HPLC (Table 3, Method 32)

Sources & evidence

ORD record
ord-60575bf3127347ae81015ab50f3ffa96
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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