Acetyl chloride → 1-(4-((5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)amino)piperidin-1-yl)ethanone

HRID 595503Notes

Reaction equation

HRID 595503 reaction equation
[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[CH:16]=[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])[C:14]([C:21]4[O:22][C:23]([NH:26][CH:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[N:24][N:25]=4)=[CH:13][N:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C1C[O:36][CH2:35][CH2:34]1.CCN(C(C)C)C(C)C.C(Cl)(=O)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:12]=[CH:13][C:14]([C:21]4[O:22][C:23]([NH:26][CH:27]5[CH2:32][CH2:31][N:30]([C:35](=[O:36])[CH3:34])[CH2:29][CH2:28]5)=[N:24][N:25]=4)=[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])[CH:16]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 89690939N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-(piperidin-4-ylamino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine

Product 1

HCID 896909411-(4-((5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)amino)piperidin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of N2-(benzo[d]thiazol-6-yl)-N4-isopropyl-5-(5-(piperidin-4-ylamino)-1,3,4-oxadiazol-2-yl)pyridine-2,4-diamine (Example 131) (40 mg, 0.08 mmol) in DCM (5 mL): THF (5 mL), added DIPEA (0.08 mmol, 1.5 equiv.) and DMAP (0.008 mmol, 0.1 equiv.) and stirred for 5 min. Added acetyl chloride (0.8 mmol, 0.8 equiv.) dropwise at 0° C. Stirred the reaction mixture at 0° C. for 1 h, the reaction temperature was raised to room temperature and stirred overnight. The reaction mixture was diluted with DCM. The DCM layer was washed with 10% NaHCO3 solution followed by water. The DCM layer was collected, dried over Na2SO4, filtered and concentrated. The material obtained was purified by prep HPLC to afford the title compound, 1-(4-((5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)amino)piperidin-1-yl)ethanone. 1H NMR: 400 MHz, CD3OD: δ 1.34 (d, J=6.40 Hz, 6H), 1.57-1.66 (m, 2H), 1.97 (s, 3H), 2.00-2.06 (m, 2H), 3.77-3.82 (m, 1H), 3.93-3.98 (m, 1H), 4.03-4.06 (m, 2H), 6.17 (s, 1H), 7.53-7.56 (m, 1H), 7.98 (d, J=8.80 Hz, 1H), 8.38 (s, 1H), 8.43 (d, J=2.00 Hz, 1H), 9.08 (s, 1H). LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.514 min; LCMS (ES-API), m/z 493.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.396 min; Purity: 99.4%.

Workup

  1. customdropwise at 0° C
  2. stirringStirred the reaction mixture at 0° C. for 1 h
  3. stirringstirred overnight
  4. washThe DCM layer was washed with 10% NaHCO3 solution
  5. customThe DCM layer was collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material obtained
  10. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-2d2c95e8f4514e1e9346b295fa45f204
Source dataset
uspto-grants-2016_01
Patent number
US09242976B2

Reaction notes

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