Pyrrolidine → 1-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-5-(1-pyrrolidinyl-carbonyl)-1H-benzimidazole

HRID 1796485Notes

Reaction equation

HRID 1796485 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14](O)=[O:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[CH:20][N:19]=2)[CH2:3][CH2:2]1.CN(C(ON1N=NC2[CH:38]=[CH:39][CH:40]=[N:41][C:36]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.N1CCCC1>CN(C=O)C>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]([N:41]4[CH2:40][CH2:39][CH2:38][CH2:36]4)=[O:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH3:26])=[CH:20][N:19]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 221814061-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carboxylic acid

Product 1

HCID 221813731-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-5-(1-pyrrolidinyl-carbonyl)-1H-benzimidazoleYield 45.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following the general procedure 20E, 1-(cyclopropylmethyl)-2-[(5-ethoxy-2-pyridinyl)methyl]-1H-benzimidazole-5-carboxylic acid (80 mg, 0.228 mmol) was dissolved in DMF (2 mL) and HATU (104 mg, 0.274 mmol) was added followed by DIPEA (48 μl, 0.274 mmol), After being stirred for 10 min, pyrrolidine was added and the resulting mixture was stirred overnight. The crude residue obtained after work-up was purified using reverse phase preparative HPLC to give a TFA salt as white solids (42 mg, 37%). 1H NMR (400 MHz, CD3OD): δ 8.18 (d, J=2.8 Hz, 1H), 7.98 (d, J=9.2 Hz, 1H), 7.87 (s, 1H), 7.72 (dd, J=9.2 Hz, J=2.0 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.46 (dd, J=9.2 Hz, J=2.8 Hz, 1H), 4.89 (s, 2H), 4.43 (d, J=6.8 Hz, 2H), 4.09 (q, J=7.2 Hz, 2H), 3.60 (t, J=7.6 Hz, 2H), 3.44 (t, J=7.6 Hz, 2H), 2.02–1.94 (m, 2H), 1.92–1.86 (m, 2H), 1.37 (t, J=7.2 Hz, 3H), 1.30–1.22 (m, 1H), 0.64–0.58 (m, 2H), 0.48–0.44 (m, 2H). MS (ESI) (M+H)+=405. Anal. Calcd for C24H28N4O2.0.8TFA.0.2H2O: C, 55.32; H, 5.12; N, 9.49. Found: C, 55.30; H, 4.91; N, 9.23.

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. customThe crude residue obtained after work-up
  3. customwas purified

Sources & evidence

ORD record
ord-92f63684db0140f690bbeb1327e9515e
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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