Diisopropylamine → HCID 178516978, compound

HRID 707434Notes

Reaction equation

HRID 707434 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:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1.C(NC(C)C)(C)C>CS(C)=O.C(Cl)Cl>[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:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[N:22]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 740542-ChloroquinazolineHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178516978HCID 178516978, compoundYield 30.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °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, 0.1099 g, 0.390 mmol), 2-chloroquinazoline (0.128 g, 0.780 mmol, Waterstone), and diisopropylamine (0.204 ml, 1.170 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO. The reaction was heated to 90° C. for 24 h. The reaction was taken up in DCM and loaded onto an Accubond SCX cartridge and washed with DCM (2×), MeOH (2×), and 2.0 ammonia in MeOH (2×). The ammonia fractions were combined and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (25 g), eluting with a gradient of 1% to 5% MeOH in CH2CL2, to provide the title compound (0.0445 g, 0.119 mmol, 30.6% yield). LCMS showed product peak at 1.511 min (m+1=374.0). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.12-1.23 (m, 4 H) 2.65 (t, J=9.29 Hz, 2 H) 2.97-3.08 (m, 1 H) 3.41-3.53 (m, 2 H) 5.30-5.42 (m, 1 H) 7.36 (t, J=6.85 Hz, 1 H) 7.69 (d, J=8.41 Hz, 1 H) 7.73-7.85 (m, 2 H) 7.92-7.99 (m, 2 H) 9.11 (br. s., 1 H)

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with DCM (2×), MeOH (2×), and 2.0 ammonia in MeOH (2×)
  3. concentrationconcentrated
  4. customchromatographed through a Biotage SNAP HP-silica gel column (25 g)
  5. washeluting with a gradient of 1% to 5% MeOH in CH2CL2

Sources & evidence

ORD record
ord-1e9baa16016c4e8fb304c3497b21229b
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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