Hydrochloric Acid → Methyl 4-({4-[(4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carbonyl]-amino}-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carboxylate

HRID 476394Notes

Reaction equation

HRID 476394 reaction equation
C(C1NC=CC=1)(OC(C)(C)C)=[O:2].[C:13]([O:17][C:18]([NH:20][C:21]1[CH:22]=[C:23]([C:27]([NH:29][C:30]2[CH:31]=[C:32]([C:36]([NH:38][C:39]3[CH:40]=[C:41]([C:45](OC)=[O:46])[N:42]([CH3:44])[CH:43]=3)=[O:37])[N:33]([CH3:35])[CH:34]=2)=[O:28])[N:24]([CH3:26])[CH:25]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.C(OC([NH:57][C:58]1[CH:59]=[C:60]([C:64]([NH:66][C:67]2[CH:68]=[C:69]([C:73]([NH:75][C:76]3[CH:77]=[C:78](C(O)=O)[N:79](C)[CH:80]=3)=[O:74])[N:70]([CH3:72])[CH:71]=2)=[O:65])[N:61]([CH3:63])[CH:62]=1)=O)(C)(C)C.CCN=C=NCCCN(C)C.O1[CH2:101][CH2:100][O:99][CH2:98]C1>CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:13]([O:17][C:18]([NH:20][C:21]1[CH:22]=[C:23]([C:27]([NH:29][C:30]2[CH:31]=[C:32]([C:36]([NH:38][C:39]3[CH:40]=[C:41]([C:45]([NH:57][C:58]4[CH:59]=[C:60]([C:64]([NH:66][C:67]5[CH:68]=[C:69]([C:73]([NH:75][C:76]6[CH:77]=[C:101]([C:100]([O:99][CH3:98])=[O:2])[N:79]([CH3:78])[CH:80]=6)=[O:74])[N:70]([CH3:72])[CH:71]=5)=[O:65])[N:61]([CH3:63])[CH:62]=4)=[O:46])[N:42]([CH3:44])[CH:43]=3)=[O:37])[N:33]([CH3:35])[CH:34]=2)=[O:28])[N:24]([CH3:26])[CH:25]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 312751,4-DioxaneHCID 10553378Methyl 4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carboxylateHCID 114316714-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carboxylic acidHCID 1545894776369-00-1

Product 1

HCID 16082635Methyl 4-({4-[(4-{[4-({4-[(4-tert-butoxycarbonylamino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carbonyl]-amino}-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-pyrrole-2-carbonyl}-amino)-1-methyl-1H-pyrrole-2-carboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

The Boc pyrrole trimer (5) (0.2 g, 0.40 mmol) in a dry round bottomed flask was treated with 4M HCl in dioxane (2.5 mL). The reaction mixture was stirred at room temperature for 30 minutes during which time a precipitate (5′) formed. The solvent was removed and the residue dried under vacuum. The residue was dissolved in dry DMF (2.5 mL) and the Boc pyrrole trimer acid (6) (0.194 g, 0.40 mmol, 1 equiv.) was added followed by EDCI (0.115 g, 0.6 mmol, 1.5 equiv.) and DMAP (0.058 g, 0.47 mmol, 1.2 equiv.). The reaction mixture was stirred for 48 hours then diluted with EtOAc (50 mL) and washed with 10% HCl solution (3×30 mL) and saturated NaHCO3 solution (3×30 mL). The organic layer was dried over MgSO4 then concentrated in vacuo to give an orange solid 0.185 g (54%). 1H NMR d6-DMSO δ 9.95 (2H, s, N—H), 9.93 (2H, s, N—H), 9.86 (1H, s, N—H), 9.08 (1H, s, Boc-N—H), 7.47 (1H, d, J=1.8 Hz, Py-H), 7.25 (1H, d, J=2.2 Hz, Py-H), 7.24 (2H, d, J=2.0 Hz, Py-H), 7.22 (1H, d, J=1.6 Hz, Py-H), 7.07 (2H, d, J=1.6 Hz, Py-H), 7.07 (1H, d, J=2.0 Hz, Py-H), 6.91 (2H, d, J=1.9 Hz, Py-H), 6.89 (1H, s, Py-H), 6.84 (1H, s, Py-H), 3.86 (3H, s, N—CH3), 3.86 (6H, s, N—CH3), 3.85 (3H, s, N—CH3), 3.84 (3H, s, N—CH3), 3.81 (3H, s, N—CH3), 3.74 (3H, s, O—CH3), 1.46 (9H, s, Boc-H).

Workup

  1. customformed
  2. customThe solvent was removed
  3. customthe residue dried under vacuum
  4. dissolutionThe residue was dissolved in dry DMF (2.5 mL)
  5. stirringThe reaction mixture was stirred for 48 hours
  6. washwashed with 10% HCl solution (3×30 mL) and saturated NaHCO3 solution (3×30 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-073921034ef443feb5f55690e81d5537
Source dataset
uspto-grants-2014_01
Patent number
US08637664B2

Reaction notes

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