1-Hydroxybenzotriazole → methyl 1-(1-((tert-butoxycarbonyl)amino)cyclopropanecarboxamido)-3-chloro-1H-pyrrole-2-carboxylate

HRID 2170177Notes

Reaction equation

HRID 2170177 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][C:4]([Cl:7])=[C:3]1[C:8]([O:10][CH3:11])=[O:9].[C:12]([O:16][C:17]([NH:19][C:20]1([C:23](O)=[O:24])[CH2:22][CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:12]([O:16][C:17]([NH:19][C:20]1([C:23]([NH:1][N:2]2[CH:6]=[CH:5][C:4]([Cl:7])=[C:3]2[C:8]([O:10][CH3:11])=[O:9])=[O:24])[CH2:22][CH2:21]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22179993Methyl 1-amino-3-chloro-1h-pyrrole-2-carboxylate

Product 1

HCID 90386158methyl 1-(1-((tert-butoxycarbonyl)amino)cyclopropanecarboxamido)-3-chloro-1H-pyrrole-2-carboxylateYield 30.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl 1-amino-3-chloro-1H-pyrrole-2-carboxylate (1.50 g, 8.59 mmol) in DCM (50 mL) was added 1-((tert-butoxycarbonyl)amino) cyclopropanecarboxylic acid (2.59 g, 12.9 mmol), HOBT (1.58 g, 10.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (2.47 g, 12.9 mmol) and DIPEA (3.00 mL, 17.2 mmol) at room temperature. The reaction mixture was stirred at room temperature for 12 h then concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed with water (2×30 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash ISCO (REDISEP®, SiO2, 12 g, 50% EtOAc/petroleum ether) to give methyl 1-(1-((tert-butoxycarbonyl)amino)cyclopropanecarboxamido)-3-chloro-1H-pyrrole-2-carboxylate (950 mg, 30.9%) as a white solid. LCMS Condition B-16: retention time 0.87 min, [M+1]=358.1. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-1.06 (m, 2H), 1.30-1.38 (m, 2H), 1.41 (s, 9H), 3.74 (s, 3H), 6.27 (s, 1H), 6.99 (d, J=2.4 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 11.08 (s, 1H).

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  3. washwashed with water (2×30 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by CombiFlash ISCO (REDISEP®, SiO2, 12 g, 50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-833c430be45c48e69c19e264176f2455
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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