Diisopropylethylamine → HCID 178518641, compound

HRID 707324Notes

Reaction equation

HRID 707324 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:15]3[N:14]=[C:13]2[O:21]C)[CH2:9]1)(C)(C)C.ClC1[S:26][C:27]2[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:28]=2[N:29]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[F:34][C:32]1[CH:31]=[CH:30][C:28]2[N:29]=[C:6]([NH:7][C@H:8]3[CH2:9][C@H:10]([N:12]4[C:16]5=[N:17][CH:18]=[CH:19][CH:20]=[C:15]5[NH:14][C:13]4=[O:21])[CH2:11]3)[S:26][C:27]=2[CH:33]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 20498702-Chloro-6-fluorobenzothiazoleHCID 178493983HCID 178493983, compound2×

Product 1

HCID 178518641HCID 178518641, compoundYield 15.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

To a glass microwave reaction vessel was added 3-(trans-3-aminocyclobutyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (intermediate 43, 0.1288 g, 0.465 mmol), 2-chloro-6-fluorobenzo[d]thiazole (0.087 g, 0.465 mmol), and diisopropylethylamine (0.283 ml, 1.627 mmol) in dry dimethylsulfoxide (1.549 ml). The vial was sealed and heated at 90° C. for 14 hours. It was allowed to cool to room temperature and the crude product purified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in acetonitrile/water, gradient 10% to 90% over 12 min) to give the desired 3-(trans-3-((6-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (26.2 mg, 0.074 mmol, 15.86% yield). M+1: 355.99. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.37-2.47 (m, 2 H) 3.25-3.34 (m, 1 H) 4.55 (d, J=5.28 Hz, 1 H) 5.20 (quin, J=8.41 Hz, 1 H) 6.99-7.12 (m, 2 H) 7.32 (dd, J=7.63, 1.17 Hz, 1 H) 7.41 (dd, J=8.80, 4.89 Hz, 1 H) 7.64 (dd, J=8.80, 2.74 Hz, 1 H) 8.00 (dd, J=5.18, 1.27 Hz, 1 H) 8.56 (d, J=6.06 Hz, 1 H) 11.15 (s, 1 H).

Workup

  1. customTo a glass microwave reaction vessel
  2. customThe vial was sealed
  3. temperatureto cool to room temperature
  4. customthe crude product purified by reverse-phase preparative HPLC (Phenomenex Gemini column, 10 micron, C18, 100 Å, 150×30 mm, 0.1% TFA in acetonitrile/water, gradient 10% to 90% over 12 min)

Sources & evidence

ORD record
ord-b1499011c98a49bab89facb1ef56f030
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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