Diisopropylamine → HCID 178481286, compound

HRID 707438Notes

Reaction equation

HRID 707438 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.Cl[C:21]1[N:25]([CH3:26])[C:24]2[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=2[N:22]=1.C(NC(C)C)(C)C>CS(C)=O>[CH:16]1([N:9]2[C:10]3=[N:15][CH:14]=[CH:13][N:12]=[C:11]3[N:7]([C@H:5]3[CH2:6][C@H:3]([NH:2][C:21]4[N:25]([CH3:26])[C:24]5[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=5[N:22]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 6630802-chloro-1-methyl-1H-1,3-benzodiazoleHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178481286HCID 178481286, compoundYield 6.7%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 0.1138 g, 0.404 mmol), 2-chloro-1-methyl-1H-benzo[d]imidazole (0.081 g, 0.485 mmol), and diisopropylamine (0.211 ml, 1.212 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (0.577 ml) and heated to 120° C. to stir for 2 days. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CNiH2O, gradient 10% to 100% over min. Fractions containing product were collected and concentrated. Residue taken up in DCM and loaded onto a Silicycle Si-carbonate cartridge to remove any salts to give the title compound (103 mg, 0.027 mmol, 6.79 yield). LCMS showed product peak at 1.57 min (m+1=376.0). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.97-1.03 (m, 2 H) 1.04-1.11 (m, 2 H) 2.47 (d, J=3.33 Hz, 1 H) 2.98 (tt, f=7.04, 3.72 Hz, 1 H) 3.27 (dt, J=13.30, 8.12 Hz, 2 H) 3.56 (s, 3 H) 4.53-4.66 (m, 1 H) 5.24 (quin, J=8.31 Hz, 1 H) 6.89-6.99 (m, 2 H) 7.02 (d, J=6.46 Hz, 1 H) 7.13-7.19 (m, 1 H) 7.19-7.25 (m, 1 H) 7.96-8.00 (m, 1 H) 8.00-8.04 (m, 1 H)

Workup

  1. customA glass microwave reaction vessel
  2. customThe crude product was purified by reverse-phase preparative HPLC
  3. additionFractions containing product
  4. customwere collected
  5. concentrationconcentrated
  6. customto remove any salts

Sources & evidence

ORD record
ord-06125c09daef4a34995f428444819e3c
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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