Water → HCID 86279293, compound

HRID 588908Notes

Reaction equation

HRID 588908 reaction equation
[C:1]([N:5]1[CH2:8][CH:7]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:31])[CH2:16][NH:17][C:18]3[CH:26]=[C:25]([CH:27]4[CH2:29][CH2:28]4)[C:24]([Cl:30])=[CH:23][C:19]=3[C:20]([NH2:22])=O)[CH2:11][CH2:10]2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].CCN(CC)CC.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>C(Cl)Cl>[C:1]([N:5]1[CH2:6][CH:7]([N:9]2[CH2:10][CH2:11][N:12]([C:15](=[O:31])[CH2:16][NH:17][C:18]3[CH:26]=[C:25]([CH:27]4[CH2:28][CH2:29]4)[C:24]([Cl:30])=[CH:23][C:19]=3[C:20]#[N:22])[CH2:13][CH2:14]2)[CH2:8]1)(=[O:4])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 90456116HCID 90456116, compound

Product 1

HCID 86279293HCID 86279293, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-((2-(4-(1-acryloylazetidin-3-yl)piperazin-1-yl)-2-oxoethyl)amino)-5-chloro-4-cyclopropylbenzamide (3 0 mg, 0.067 mmol) and Et3N (41 mg, 0.404 mmol) in DCM (10 mL) at RT, trifluoroacetic anhydride (56 mg, 0.268 mmol) was added. The resulting mixture was stirred at RT for 0.5 h, poured into water and then extracted with dichloromethane. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (1-4% methanol/dichloroethane) to afford the desired product (20 mg, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ: 7.60 (s, 1H), 6.34-6.30 (m, 1H), 6.27 (s, 1H), 6.12-6.07 (m, 1H), 6.01-5.99 (t, J=4 Hz, 1H), 5.69-5.65 (m, 1H), 4.26-4.22 (m, 1H), 4.07-4.04 (m, 3H), 3.96-3.92 (m, 1H), 3.80-3.76 (m, 1H), 3.53-3.51 (m, 4H), 3.19-3.13 (m, 1H), 2.45-2.30 (m, 4H), 2.16-2.09 (m, 1H), 1.08-1.03 (m, 2H), 0.87-0.80 (m, 2H). ESI-MS m/z: 428.4[M+H]+.

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel (1-4% methanol/dichloroethane)

Sources & evidence

ORD record
ord-37d41a81935242b8b1dfb37285fcedac
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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