O-Phenylenediamine → 2-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-benzimidazole

HRID 272989Notes

Reaction equation

HRID 272989 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22](O)=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH2:32]>>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3([C:22]4[NH:32][C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=5[N:25]=4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:14][CH:15]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

3

Reactant 2

HCID 7243O-PhenylenediamineHCID 598374194-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylic acid

Product 1

HCID 598373462-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-yl}-1H-benzimidazoleYield 1%

Conditions

Temperature
130 °C

Procedure

A mixture of 4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carboxylic acid (400 mg, 1.20 mmol), 1,2-diaminobenzene (129 mg, 1.20 mmol) and polyphosphoric acid (2 g) was heated at 130° C. for 2 days. The cooled reaction mixture was partitioned between dichloromethane (20 ml) and aqueous ammonia (20 ml). The aqueous layer was further extracted with dichloromethane (2×50 ml). The organic layers were combined, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC on Fraction-Lynx® eluting with water:acetonitrile:TFA (95:5:0.1) to provide the title compound (3.5 mg, 1%). 1H NMR (400 MHz, CDCl3) δ 1.92-1.96 (m, 2H), 2.06-2.21 (m, 4H), 2.40-2.46 (m, 2H), 2.96-3.00 (m, 4H), 3.05-3.09 (m, 2H), 3.16-3.20 (m, 2H), 3.57-3.65 (m, 4H), 3.93 (d, 2H), 5.45 (d, 2H), 7.06 (d, 2H), 7.45 (d, 2H), 7.71-7.74 (m, 2H). LCMS ESI+ m/z 406 [MH]+.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between dichloromethane (20 ml) and aqueous ammonia (20 ml)
  3. extractionThe aqueous layer was further extracted with dichloromethane (2×50 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative HPLC on Fraction-Lynx®
  8. washeluting with water:acetonitrile:TFA (95:5:0.1)

Sources & evidence

ORD record
ord-30997f94c5c54b0bbb3aa15c8b42bd40
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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