1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (11S,11aS)-allyl 7-methoxy-8-(4-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-4-oxobutoxy)-5-oxo-11-((tetrahydro-2H-pyran-2-yl)oxy)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10(5H)-carboxylate
Reaction equation
[CH2:1]([O:4][C:5]([N:7]1[C:13]2[CH:14]=[C:15]([O:20][CH2:21][CH2:22][CH2:23][C:24]([NH:26][C:27]3[CH:28]=[C:29]([C:33]([OH:35])=O)[N:30]([CH3:32])[CH:31]=3)=[O:25])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[C:11](=[O:36])[N:10]2[CH2:37][CH2:38][CH2:39][C@H:9]2[C@@H:8]1[O:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][O:42]1)=[O:6])[CH:2]=[CH2:3].CCN=C=NCCCN(C)C.Cl.C(OC(N1C2C=C(OCCCC(O)=O)C(OC)=CC=2C(=O)N2CCCC2C1OC1CCCCO1)=O)C=C.[NH2:96][C:97]1[CH:102]=[CH:101][C:100]([C:103]2[CH:104]=[C:105]([C:109]([O:111][CH3:112])=[O:110])[N:106]([CH3:108])[CH:107]=2)=[CH:99][CH:98]=1>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:19][O:18][C:16]1[C:15]([O:20][CH2:21][CH2:22][CH2:23][C:24]([NH:26][C:27]2[CH:28]=[C:29]([C:33](=[O:35])[NH:96][C:97]3[CH:102]=[CH:101][C:100]([C:103]4[CH:104]=[C:105]([C:109]([O:111][CH3:112])=[O:110])[N:106]([CH3:108])[CH:107]=4)=[CH:99][CH:98]=3)[N:30]([CH3:32])[CH:31]=2)=[O:25])=[CH:14][C:13]2[N:7]([C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[C@@H:8]([O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)[C@@H:9]3[CH2:39][CH2:38][CH2:37][N:10]3[C:11](=[O:36])[C:12]=2[CH:17]=1Participants
Reactant 4
HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride
HCID 58326676Methyl 4-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carboxylate
HCID 732365854-(10-(allyloxycarbonyl)-7-methoxy-5-oxo-11-(tetrahydro-2H-pyran-2-yloxy)-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butanoic acid
HCID 1180612204-(4-(((11S,11aS)-10-((allyloxy)carbonyl)-7-methoxy-5-oxo-11-((tetrahydro-2H-pyran-2-yl)oxy)-2,3,5,10,11,11a-hexahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)butanamido)-1-methyl-1H-pyrrole-2-carboxylic acidProduct 1
Reagents, catalysts & solvents 2
Procedure
A solution of Alloc-THP protected PBD-Py acid 14a (150 mg, 0.23 mmol, 1.0 equivalent) was dissolved in DMF. EDCl (2.49 g, 13.02 mmol, 2.0 eq) and DMAP (1.989 g, 16.28 mmol, 2.5 eq) were added to the stirred solution of 13 at room temperature and the mixture was allowed to stir for 30 minutes after which the MPB-ester 7 (67.83 mg, 0.29 mmol, 1.25 eq) was added. The reaction mixture was allowed to stir for a further 3 hour at which point TLC showed completion of reaction. The reaction was quenched by pouring it onto a mixture of ice/water mixture and the resulting mixture was extracted with ethyl acetate (3×150 mL). The combined extracts were sequentially washed with citric acid (50 mL), saturated aqueous NaHCO3 (50 mL), water (50 mL), brine (50 mL) and finally dried over MgSO4. Excess ethyl acetate was evaporated by rotary evaporator under reduced pressure and the crude product was directly used in the next step without further purification. m/z (+EI) calc. for C45H52N6O11 (M)+ 852.93. found 854.87 ([M+H]+.
Workup
- additionwas added
- customcompletion of reaction
- customThe reaction was quenched
- additionby pouring it
- additiononto a mixture of ice/water mixture
- extractionthe resulting mixture was extracted with ethyl acetate (3×150 mL)
- washThe combined extracts were sequentially washed with citric acid (50 mL), saturated aqueous NaHCO3 (50 mL), water (50 mL), brine (50 mL)
- dry with materialfinally dried over MgSO4
- customExcess ethyl acetate was evaporated by rotary evaporator under reduced pressure
- customthe crude product was directly used in the next step without further purification
Sources & evidence
- ORD record
- ord-1801350adb164cad916a49341c839b8b
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376440B2
Reaction notes
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