Diisopropylethylamine → HCID 178461907, compound

HRID 243283Notes

Reaction equation

HRID 243283 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=[C:15]2[C@@H:23]([NH2:25])[CH3:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:27]1[N:35]=[CH:34][N:33]=[C:32]2[C:28]=1[N:29]=[CH:30][NH:31]2.CCN(C(C)C)C(C)C>C(O)CCC>[N:35]1[C:27]([NH:25][C@H:23]([C:15]2[N:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]=2)[CH3:24])=[C:28]2[C:32]([NH:31][CH:30]=[N:29]2)=[N:33][CH:34]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68157390HCID 68157390, compoundHCID 178478393HCID 178478393, compound

Product 1

HCID 178461907HCID 178461907, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-[2-((S)-1-aminoethyl)benzoimidazol-1-yl]piperidine-1-carboxylic acid tertbutyl ester from Example 6 (202 mg), 6-chloro-9H-purine (91 mg, 0.586 mmol) and DIPEA (0.2 mL, 1.17 mmol) in n-butanol (1 mL) was stirred in a sealed tube for 3 h at 120° C. After cooling to RT, the crude reaction mixture was partitioned between EtOAc and water. The organic layer was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) and then triturated with diethyl ether affording 112 as a pale brown solid (113 mg, 38% over two steps). LCMS: RT 3.24 min [M+H]+ 463.2. 1H NMR (CDCl3, 400 MHz): δ 8.54 (1H, s), 7.98 (1H, s), 7.78 (1H, d, J=7.55 Hz), 7.49 (1H, d, J=7.36 Hz), 7.28-7.07 (3H, m), 6.13 (1H, br), 4.89-4.78 (1H, m), 4.47-4.04 (2H, m), 2.97-2.78 (1H, m), 2.60-2.26 (3H, m), 1.99-1.62 (6H, m), 1.49 (9H, s)

Workup

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. customwas partitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  8. customtriturated with diethyl ether affording 112 as a pale brown solid (113 mg, 38% over two steps)

Sources & evidence

ORD record
ord-104c0d02cd444d87aebb1ab47e7ec5b2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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