Diisopropylamine → HCID 178516977, compound

HRID 707417Notes

Reaction equation

HRID 707417 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[S:22][C:23]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:24]=2[N:25]=1.C(NC(C)C)(C)C>CN(C1C=CN=CC=1)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[S:22][C:23]5[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:24]=5[N:25]=4)[CH2:4]3)[C:8]2=[O:19])[CH2:17][CH2:18]1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 20498702-Chloro-6-fluorobenzothiazoleHCID 178479284HCID 178479284, compound2×

Product 1

HCID 178516977HCID 178516977, compoundYield 33.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent

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, 0.1283 g, 0.455 mmol), 2-chloro-6-fluorobenzo[d]thiazole (0.094 g, 0.501 mmol, Step 1), DMAP (0.056 g, 0.455 mmol, Sigma-Aldrich Chemical Company, Inc.), and diisopropylamine (0.238 ml, 1.366 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO (1.518 ml) and heated to 90° C. for 20 h. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 90% over 12 min. Fractions containing product peak were concentrated in vacuo. The product was taken up in DCM and loaded onto a Silicyle Si-carbonate cartridge to remove any salts to give the title compound (61.2 mg, 0.154 mmol, 33.9% yield). LCMS showed product peak at 1.732 min (m+1=397.0).

Workup

  1. customA glass microwave reaction vessel
  2. customThe crude product was purified by reverse-phase preparative HPLC
  3. customover 12 min
  4. additionFractions containing product peak
  5. concentrationwere concentrated in vacuo
  6. customto remove any salts

Sources & evidence

ORD record
ord-e6d920bc056c4cbca63c04fb9f6eeab9
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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