Diisopropylethylamine → HCID 59837389, compound

HRID 272986Notes

Reaction equation

HRID 272986 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([CH2:22][NH2:23])[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.[CH3:24][N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1S(O)(=O)=O.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:24][N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[NH:23][CH2:22][C:16]1([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:11][CH:12]=2)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 27247881-methyl-1H-benzimidazole-2-sulfonic acidHCID 11645410(4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine

Product 1

HCID 59837389HCID 59837389, compoundYield 16.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
155 °C

Procedure

A mixture of {4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine (150 mg, 0.47 mmol), 1-methylbenzimidazole-2-sulfonic acid (83.4 mg, 0.39 mmol) and N,N-diisopropylethylamine (175 μl, 0.98 mmol) in acetonitrile (1.5 ml) was heated at 155° C. in the Smith Personal Synthesiser for 2400 seconds and then a further 900 seconds. The reaction mixture was partitioned between dichloromethane (10 ml) and saturated aqueous sodium bicarbonate solution (10 ml). The organic layer was dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 95:5:0.5 by volume) to provide the title compound (29 mg, 14%). 1H NMR (400 MHz, CD3OD) δ 1.83-1.86 (m, 4H), 1.96-2.02 (m, 4H), 2.19 (d, 2H), 2.63-2.66 (m, 4H), 2.70 (t, 2H), 3.41 (s, 3H), 3.50 (t, 2H), 3.57 (s, 2H), 3.79-3.82 (m, 2H), 3.97 (t, 2H), 6.91 (d, 2H), 6.97-7.02 (m, 2H), 7.08 (d, 1H), 7.22 (d, 1H), 7.36 (d, 2H). LRMS APCI+ m/z 449 [MH]+.

Workup

  1. customa further 900 seconds
  2. customThe reaction mixture was partitioned between dichloromethane (10 ml) and saturated aqueous sodium bicarbonate solution (10 ml)
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 95:5:0.5 by volume)

Sources & evidence

ORD record
ord-415124cff868477488ff8546b8b914a9
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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