Pyrrole-2-Carboxylic Acid → (7S,10S,13S)-10-Isopropyl-9,12-dioxo-13-[(1H-pyrrole-2-carbonyl)-amino]-2-oxa-8,11-diaza-bicyclo[13.2.2]nonadeca-1(18),15(19),16-triene-7-carboxylic acid methyl ester

HRID 2371328

Reaction equation

HRID 2371328 reaction equation
Cl.[CH3:2][O:3][C:4]([C@H:6]1[NH:22][C:21](=[O:23])[C@H:20]([CH:24]([CH3:26])[CH3:25])[NH:19][C:18](=[O:27])[C@@H:17]([NH2:28])[CH2:16][C:15]2=[CH:29][CH:30]=[C:12]([CH:13]=[CH:14]2)[O:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5].[NH:31]1[CH:35]=[CH:34][CH:33]=[C:32]1[C:36](O)=[O:37].CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O.C(Cl)CCl>[CH3:2][O:3][C:4]([C@H:6]1[NH:22][C:21](=[O:23])[C@H:20]([CH:24]([CH3:26])[CH3:25])[NH:19][C:18](=[O:27])[C@@H:17]([NH:28][C:36]([C:32]2[NH:31][CH:35]=[CH:34][CH:33]=2)=[O:37])[CH2:16][C:15]2=[CH:29][CH:30]=[C:12]([CH:13]=[CH:14]2)[O:11][CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5]

Participants

8

Reactant 4

HCID 12473Pyrrole-2-Carboxylic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 86650244(7S,10S,13S)-13-Amino-10-isopropyl-9,12-dioxo-2-oxa-8,11-diaza-bicyclo[13.2.2]nonadeca-1-(18),15(19),16-triene-7-carboxylic acid methyl ester hydrogen chloride salt

Product 1

HCID 66846964(7S,10S,13S)-10-Isopropyl-9,12-dioxo-13-[(1H-pyrrole-2-carbonyl)-amino]-2-oxa-8,11-diaza-bicyclo[13.2.2]nonadeca-1(18),15(19),16-triene-7-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Amine 47 (0.37 g) was dissolved in anhydrous DMF (5 mL). 1H-pyrrole-carboxylic acid (0.11 g), DIPEA (0.72 mL), EDC (0.25 g) and HOBt (0.2 g) were added and the reaction mixture was stirred at rt for 18 h before being partitioned between chloroform and 1M hydrochloric acid. The aqueous phase was extracted three more times with chloroform and the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification was achieved using flash chromatography, eluting with a gradient of 20% EtOAc/(50/70) petroleum ether to EtOAc to yield an off-white solid, 279 mg, 55%. Rf=0.15 (20% EtOAc/(50/70) petroleum ether).

Workup

  1. custombefore being partitioned between chloroform and 1M hydrochloric acid
  2. extractionThe aqueous phase was extracted three more times with chloroform
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification
  7. washeluting with a gradient of 20% EtOAc/(50/70) petroleum ether to EtOAc
  8. customto yield an off-white solid, 279 mg, 55%

Sources & evidence

ORD record
ord-d7ddace1f2f949658e3e499fc0510082
Source dataset
uspto-grants-2014_04
Patent number
US08710178B2

Linked notes

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