Hydrochloric Acid → 1-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbonyl)-1H-benzimidazole

HRID 1796479Notes

Reaction equation

HRID 1796479 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][CH: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.Cl>CN(C=O)C.C(OCC)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][CH:19]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22181336HCID 22181336, compound

Product 1

HCID 221812751-(Cyclopropylmethyl)-2-(4-ethoxybenzyl)-5-(1-pyrrolidinylcarbonyl)-1H-benzimidazoleYield 89.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Following the general procedure 20E, 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carboxylic acid (80 mg, 0.228 mmol) was dissolved in DMF (2 mL) and then HATU (104 mg, 0.274 mmol) was added followed by DIPEA (48 μL, 0.274 mmol), After being stirred for 10 min, pyrrolidine (0.456 mmol) was added and the resulting mixture was stirred overnight. The crude residue after work-up was purified by silica gel column chromatography to give pure product which was treated with 1 M HCl solution in diethyl ether to form a HCl salt as white solids (82 mg, 79%). 1H N (400 MHz, CD3OD): δ 7.85 (s, 1H), 7.59 (d, J=8.6 Hz, 1H), 7.48 (d, J=8.6 Hz, 1H), 7.18 (d, J=8.1 Hz, 2H), 6.87 (d, J=8.1 Hz, 2H), 4.32 (s, 2H), 4.07 (d, J=6.8 Hz, 2H), 4.00 (q, J=7.6 Hz, 2H), 3.64 (t, J=. 7.2 Hz, 2H), 3.53 (t, J=7.2 Hz, 2H), 2.06–1.96 (m, 2H), 1.96–1.85 (m, 2H), 1.36 (t, J=7.6 Hz, 3H), 1.10–1.04 (m, 1H), 0.52–0.46 (m, 2H), 0.34–0.28 (m, 2H). MS (ESI) (M+H)+=404. Anal. Calcd for C25H29N3O2.1.5HCl: C, 65.53; H, 6.71; N, 9.17. Found: C, 65.48; H, 6.77; N, 8.75.

Workup

  1. stirringthe resulting mixture was stirred overnight
  2. customThe crude residue after work-up was purified by silica gel column chromatography
  3. customto give pure product which

Sources & evidence

ORD record
ord-a546e29150934642a7b4067f7d32d648
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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