Potassium Carbonate → HCID 86279022, compound

HRID 588886Notes

Reaction equation

HRID 588886 reaction equation
[C:1]([N:5]1[CH2:8][CH:7]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17]C(C)(C)C)=O)[CH2:11][CH:10]2[C:22](=[O:24])[NH2:23])[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].[Cl:25][C:26]1[C:31]([CH:32]2[CH2:34][CH2:33]2)=[CH:30][C:29]([NH:35][CH2:36]C(O)=O)=[C:28]([OH:40])[CH:27]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C([O-])([O-])=O.[K+].[K+]>Cl.CO.CN(C=O)C>[C:1]([N:5]1[CH2:6][CH:7]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:17])[CH2:36][NH:35][C:29]3[CH:30]=[C:31]([CH:32]4[CH2:33][CH2:34]4)[C:26]([Cl:25])=[CH:27][C:28]=3[OH:40])[CH2:11][CH:10]2[C:22]([NH2:23])=[O:24])[CH2:8]1)(=[O:4])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 90455895HCID 90455895, compoundHCID 117610523HCID 117610523, compound

Product 1

HCID 86279022HCID 86279022, compoundYield 77.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

A mixture of tert-butyl 4-(1-acryloylazetidin-3-yl)-3-carbamoylpiperazine-1-carboxylate (120 mg, 0.35 mmol) in HCl/MeOH (2.86 M, 10 mL) was stirred at RT for 1 h. The mixture was concentrated in vacuo to afford the crude residue. It was dissolved in DMF (5 mL) at 0° C., 2-(4-chloro-5-cyclopropyl-2-hydroxyphenylamino)acetic acid (31 mg, 0.427 mmol), BOP (206 mg, 0.466 mmol) and K2CO3 (150 mg, 1.164 mmol) were added and the resulting mixture was stirred at RT for 1 h. The mixture was partitioned between ethyl acetate and water. The organic layer was washed brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=20:1) to afford the desired product (126 mg, 75% yield, 2 steps). 1H NMR (400 MHz, DMSO-d6) δ: 9.63 (bs, 1H), 7.53 (d, 1H), 7.26-6.94 (m, 2H), 6.67 (s, 1H), 6.34-6.27 (m, 1H), 6.10 (m, 2H), 5.68 (d, J=10.4, 1H), 5.08 (m, 1H), 4.30 (m, 2H), 3.93 (m, 6H), 3.52 (m, 2H), 3.29 (m, 1H), 3.15 (m, 1H), 3.06 (m, 1H), 2.47 (m, 1H), 1.98 (m, 1H), 0.87 (m, 2H), 0.64 (m, 2H). ESI-MS m/z: 462.5[M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto afford the crude residue
  3. stirringthe resulting mixture was stirred at RT for 1 h
  4. customThe mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-51954bd072c246ad8418e8910869b708
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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