(S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate → (S)-2-(1-aminoethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide

HRID 2036575Notes

Reaction equation

HRID 2036575 reaction equation
[CH:1]1([NH:4][C:5]2[C:10]([C:11](=[O:14])[NH:12][CH3:13])=[CH:9][CH:8]=[CH:7][C:6]=2[NH:15][C:16](=O)[C@@H:17]([NH:19]C(=O)OC(C)(C)C)[CH3:18])[CH2:3][CH2:2]1>CC(O)=O>[NH2:19][C@H:17]([C:16]1[N:4]([CH:1]2[CH2:3][CH2:2]2)[C:5]2[C:10]([C:11]([NH:12][CH3:13])=[O:14])=[CH:9][CH:8]=[CH:7][C:6]=2[N:15]=1)[CH3:18]

Participants

3

Reactant 1

HCID 58459271(S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate

Product 1

HCID 58459136(S)-2-(1-aminoethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A stirred solution of (S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate (1.1 g, 2.9 mmol) in AcOH (30 mL) was heated at 65° C. for 2 h, and cooled to rt. After concentrating under reduced pressure, the residue was subjected to 4 M HCl in 1,4-dioxane (20 mL) and stirred at rt for 40 min. The mixture was concentrated under reduced pressure and dissolved in water (5 mL) basified with 1 N NaOH to pH 9.5. The mixture was concentrated and triturated with MeOH-CDM (1:1). The crude product was purified by column chromatography on a silica gel column using DCM-MeOH—NH4OH (9:1:0.05) as eluent to give (S)-2-(1-aminoethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide: 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 7.23 (dd, J=8, 8 Hz, 1H), 6.09 (br, 1H), 4.61 (t, J=8 Hz, 1H), 3.53-3.46 (m, 1H), 3.11 (d, J=4 Hz, 3H), 1.63 (d, J=8 Hz, 3H), 1.22-1.07 (m, 2H), 1.02-0.94 (m, 1H), 0.90-0.83 (m, 1H); LC-MS (ESI) m/z 259.1 [M+H]+.

Workup

  1. concentrationAfter concentrating under reduced pressure
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutiondissolved in water (5 mL)
  4. concentrationThe mixture was concentrated
  5. customtriturated with MeOH-CDM (1:1)
  6. customThe crude product was purified by column chromatography on a silica gel column

Sources & evidence

ORD record
ord-df6f54e3fd074c1d85281f8da3a4d228
Source dataset
uspto-grants-2013_11
Patent number
US08575183B2

Reaction notes

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