Sodium Sulfite → 3-((R)-8-iodo-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 519142Notes

Reaction equation

HRID 519142 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:31])([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)[CH:14]=[CH:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I:32]N1C(=O)CCC1=O.S([O-])([O-])=O.[Na+].[Na+]>C1COCC1>[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]([I:32])=[CH:13]2)([CH3:31])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24437Sodium SulfiteHCID 120273N-IodosuccinimideHCID 867275273-methyl-3-((R)-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 867275343-((R)-8-iodo-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 30.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-methyl-3-((R)-1-methyl-2-oxo-1,2,3,5-tetrahydro-6-oxa-3,4,10,11b-tetraaza-cyclopenta[b]phenanthren-10-yl)-azetidine-1-carboxylic acid tert-butyl ester (Example #148, Step J, 1 g, 2.35 mmol) in THF (20 mL) was added 1-iodopyrrolidine-2,5-dione (0.582 g, 2.59 mmol) in portions at −5-0° C. The reaction mixture was stirred at 0° C. for 3 h. Saturated aqueous sodium sulphite solution (5 mL) was added to quench the reaction and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether) to give 3-((R)-8-iodo-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 (0.4 g, 30%) as a yellow solid. 1H NMR (400 MHz, methanol-d4): δ 7.39 (s, 1H), 6.97 (s, 1H), 6.89 (s, 1H), 4.97 (m, 1H), 4.53 (d, J=8.5 Hz, 2H), 4.59 (m, 2H), 4.54 (m, 2H), 4.29 (m, 2H), 1.81 (s, 3H), 1.51-1.48 (m, 12H). LC/MS (Table 1, Method 2) Rt=1.279 min.; MS m/z: 552 [M+H]+.

Workup

  1. customto quench
  2. customthe reaction
  3. customthe solvent was removed in vacuo
  4. customThe residue was purified by column chromatography on silica gel (eluting with 10%˜100% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-576aae3ffaf14421b0b178cc1fca44db
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

Loading…