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

HRID 476392Notes

Reaction equation

HRID 476392 reaction equation
N1C=CC=C1.[C:6]([O:10][C:11]([NH:13][C:14]1[CH:15]=[C:16]([C:20]([NH:22][C:23]2[CH:24]=[C:25](C(OC)=O)[N:26]([CH3:28])[CH:27]=2)=[O:21])[N:17]([CH3:19])[CH:18]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].Cl.[C:34](C1NC=CC=1)([O:36][C:37](C)(C)C)=[O:35].CCN=[C:49]=[N:50][CH2:51][CH2:52][CH2:53][N:54]([CH3:56])[CH3:55].[OH-:57].[Na+]>O1CCOCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O.CO>[C:6]([O:10][C:11]([NH:13][C:14]1[CH:15]=[C:16]([C:20]([NH:22][C:23]2[CH:24]=[C:25]([C:49]([NH:50][C:51]3[CH:52]=[C:53]([C:34]([O:36][CH3:37])=[O:35])[N:54]([CH3:55])[CH:56]=3)=[O:57])[N:26]([CH3:28])[CH:27]=2)=[O:21])[N:17]([CH3:19])[CH:18]=1)=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8027PyrroleHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 10523563methyl 4-(4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylateHCID 1545894776369-00-1

Product 1

HCID 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-carboxylateYield 48%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

The Boc protected pyrrole dimer (3) (0.25 g, 0.66 mmol) was placed in a dry round bottomed flask and treated with 4M HCl in dioxane (5 mL). The resulting solution became cloudy over a period of 30 minutes. The solvent was removed in vacuo to give a yellow solid (3′) which was then dried under vacuum. The residue was dissolved in dry DMF (9 mL) and the Boc pyrrole acid (2) (0.176 g, 0.726 mmol, 1.1 equiv.) was added followed by EDCI (0.191 g, 0.99 mmol, 1.5 equiv.) and DMAP (0.097 g, 0.79 mmol, 1.2 equiv.). The reaction mixture was stirred at room temperature for 18 hours then diluted with EtOAc (50 mL) and washed with 1M HCl soln (3×50 mL), then saturated NaHCO3 solution (3×50 mL), dried over MgSO4 then concentrated in vacuo to give a tan foam. This solid was suspended in a 1:1 mixture of MeOH and 1M NaOH solution (40 mL) and stirred at room temp for 30 minutes. EtOAc was added and the organic layer washed with saturated NaHCO3 solution (3×50 mL) and dried over MgSO4. Concentration in vacuo gave an off white foam 0.160 g (48%). Mp 134° C. (lit 131-133° C.); 1H NMR d6-DMSO δ 9.90 (1H, s, N—H), 9.86 (1H, s, N—H), 9.13 (1H, s, Boc-N—H), 7.46 (1H, d, J=1.9 Hz, Py-H), 7.21 (1H, d, J=1.7 Hz, Py-H), 7.06 (1H, d, J=1.7 Hz, Py-H), 6.91 (1H, s, Py-H), 6.90 (1H, s, Py-H), 6.85 (1H, s, Py-H), 3.84 (6H, s, N—CH3), 3.81 (3H, s, N—CH3), 3.74 (3H, s, O—CH3), 1.46 (9H, s, Boc-H).

Workup

  1. customwas placed in a dry round bottomed flask
  2. customof 30 minutes
  3. customThe solvent was removed in vacuo
  4. customto give a yellow solid (3′) which
  5. customwas then dried under vacuum
  6. dissolutionThe residue was dissolved in dry DMF (9 mL)
  7. washwashed with 1M HCl soln (3×50 mL)
  8. dry with materialsaturated NaHCO3 solution (3×50 mL), dried over MgSO4
  9. concentrationthen concentrated in vacuo
  10. customto give a tan foam
  11. stirringstirred at room temp for 30 minutes
  12. washthe organic layer washed with saturated NaHCO3 solution (3×50 mL)
  13. dry with materialdried over MgSO4
  14. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-0b6baf72c4994ab3ab5bbea3dbe3e531
Source dataset
uspto-grants-2014_01
Patent number
US08637664B2

Reaction notes

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