2-chloro-N,N-dimethylacetamide → HCID 178461912, compound

HRID 243325Notes

Reaction equation

HRID 243325 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:2]1.Cl[CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31].CCN(C(C)C)C(C)C>>[N:27]1[C:19]([NH:18][C@H:16]([C:8]2[N:7]([C@@H:3]3[CH2:4][CH2:5][CH2:6][N:1]([CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31])[CH2:2]3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH3:17])=[C:20]2[C:24]([NH:23][CH:22]=[N:21]2)=[N:25][CH:26]=1

Participants

4

Reactant 3

HCID 758862-chloro-N,N-dimethylacetamideHCID 81531DiisopropylethylamineHCID 178461909HCID 178461909, compound

Product 1

HCID 178461912HCID 178461912, compoundYield 4.3%

Conditions

Temperature
70 °C

Procedure

A mixture of [(S)-1-((R)-1-piperidin-3-yl-1H-benzoimidazol-2-yl)ethyl]-(9H-purin-6-yl)amine from Example 16 (150 mg, 0.414 mmol), 2-chloro-N,N-dimethylacetamide (43 μL, 0.414 mmol) and DIPEA (215 μL, 1.24 mmol) in IMS (2 mL) was stirred in a sealed vial at 70° C. for 20 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM) followed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-50% 0.1% NH4OH in acetonitrile/water). The product containing fractions were concentrated in vacuo affording 151 as a white solid (8 mg, 4%). LCMS: RT 1.87 min [M+H]+ 448.1. 1H NMR (DMSO, 400 MHz): δ 8.24 (1H, s), 8.10 (1H, s), 7.95 (1H, bs), 7.73-7.68 (1H, m), 7.65-7.58 (1H, m), 7.21-7.12 (2H, m), 4.66-4.55 (1H, m), 3.22 (2H, s), 3.06-2.88 (6H, m), 2.80 (3H, s), 2.75-2.68 (1H, m), 2.21 (1H, t, J=11.73 Hz), 2.10-1.96 (1H, m), 1.77-1.64 9 4 H, m), 1.55 (1H, bd, J=13.18 Hz), 1.13-0.98 (1H, m)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
  4. customfollowed by HPLC purification (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-50% 0.1% NH4OH in acetonitrile/water)
  5. additionThe product containing fractions
  6. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-5f72851aeb274848aa942fbc042a185d
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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