Triethylamine → Methyl 3-[4-({3-[bis(4-methoxyphenyl)phenylmethoxy]propyl}-{4-[(2-chloro-4-nitrophenyl)diazenyl]phenyl}amino)butanoyl]pyrrolo[4,5-e]indoline-7-carboxylate

HRID 481178Notes

Reaction equation

HRID 481178 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:56]2[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=2)([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[O:10][CH2:11][CH2:12][CH2:13][N:14]([C:32]2[CH:37]=[CH:36][C:35]([N:38]=[N:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][C:41]=3[Cl:49])=[CH:34][CH:33]=2)[CH2:15][CH2:16][CH2:17][C:18](OC2C(F)=C(F)C(F)=C(F)C=2F)=[O:19])=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH:71]1[C:75]2=[C:76]3[C:80](=[CH:81][CH:82]=[C:74]2[NH:73][CH:72]=1)[NH:79][CH:78]([C:83]([O:85][CH3:86])=[O:84])[CH2:77]3>CN(C=O)C>[CH3:63][O:62][C:59]1[CH:60]=[CH:61][C:56]([C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)([C:50]2[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=2)[O:10][CH2:11][CH2:12][CH2:13][N:14]([C:32]2[CH:37]=[CH:36][C:35]([N:38]=[N:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][C:41]=3[Cl:49])=[CH:34][CH:33]=2)[CH2:15][CH2:16][CH2:17][C:18]([N:73]2[C:74]3[C:75](=[C:76]4[C:80](=[CH:81][CH:82]=3)[NH:79][CH:78]([C:83]([O:85][CH3:86])=[O:84])[CH2:77]4)[CH:71]=[CH:72]2)=[O:19])=[CH:57][CH:58]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66717311Methyl pyrrolo[4,5-e]indoline-7-carboxylateHCID 865847202,3,4,5,6-Pentafluorophenyl 4-({3-[bis(4-methoxyphenyl)phenylmethoxy]propyl}{4-[(2-chloro-4-nitrophenyl)diazenyl]phenyl}amino)butanoate

Product 1

HCID 86587108Methyl 3-[4-({3-[bis(4-methoxyphenyl)phenylmethoxy]propyl}-{4-[(2-chloro-4-nitrophenyl)diazenyl]phenyl}amino)butanoyl]pyrrolo[4,5-e]indoline-7-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 22 (3.0 g, 3.37 mmol) in 15 mL anhydrous DMF is added triethylamine (0.75 mL) followed by methyl pyrrolo[4,5-e]indoline-7-carboxylate (Boger, et al., J. Org. Chem. 52:1521 (1987)) (0.8 g, 3.7 mmol). The resultant solution is stored at room temperature for 20 h. The reaction is analyzed by HPLC to confirm its completeness. DMF is removed on a rotary evaporator equipped with an oil pump. The residue, dark syrup is suspended in 50% ethylacetate/hexanes (˜25 mL). The mixture is sonicated to initiate the crystallization. The crystals are stirred for 15 min, collected by filtration on a sintered glass funnel, washed with methanol (2×30 mL) and dried under vacuum. The yield of the desired product is 2.7 g (87%) as a deep-purple solid. 1H NMR (DMSO-d6) δ11.93 (d, J=1.7 Hz, indole NH, 1H), 8.43 (d, J=2.5 Hz, aromatic proton, 1H), 8.3-8.2 (m, aromatic protons, 2H), 7.85-7.75 (m, aromatic protons, 3H), 7.45-7.18 (m, aromatic protons, 10H), 7.05 (d, J=1.8 Hz, aromatic proton, 1H), 6.97 (d, J=9 Hz, aromatic protons, 2H), 6.87 (d, J=9 Hz, aromatic protons, 4H), 4.12 (t, J=8 Hz, aliphatic protons, 2H), 3.87 (s, ester CH3, 3H), 3.71 (s, CH3, 6H), 3.60 (br t, aliphatic protons, 2H), 3.45 (br t, aliphatic protons, 2H), 3.29 (br t, aliphatic protons, 2H), 3.08 (t, J=5 Hz, aliphatic protons, 2H), 2.5 (br t, obscured by DMSO signal, aliphatic protons, 2H), 1.88 (br m, aliphatic protons, 4H).

Workup

  1. customDMF is removed on a rotary evaporator
  2. customequipped with an oil pump
  3. customThe mixture is sonicated
  4. customthe crystallization
  5. filtrationcollected by filtration on a sintered glass funnel
  6. washwashed with methanol (2×30 mL)
  7. customdried under vacuum

Sources & evidence

ORD record
ord-10876c480fda4b28935c09f951d2e173
Source dataset
uspto-grants-2003_11
Patent number
US06653473B2

Reaction notes

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