Acrylic Acid → HCID 90461841, compound

HRID 588879Notes

Reaction equation

HRID 588879 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([NH:11][CH2:12][C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH:21]3[CH2:24][N:23]([C:25]([O:27]C(C)(C)C)=O)[CH2:22]3)[CH2:17][CH2:16]2)=[O:14])=[C:4]([O:32][CH3:33])[CH:3]=1.[C:34](O)(=O)[CH:35]=C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>Cl.CO.CN(C=O)C>[Cl:1][C:2]1[C:7]([CH:8]([CH3:9])[CH3:10])=[CH:6][C:5]([NH:11][CH2:12][C:13]([N:15]2[CH2:16][CH2:17][N:18]([CH:21]3[CH2:24][N:23]([C:25](=[O:27])[CH:34]=[CH2:35])[CH2:22]3)[CH2:19][CH2:20]2)=[O:14])=[C:4]([O:32][CH3:33])[CH:3]=1

Participants

7

Reactant 4

HCID 6581Acrylic AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 90455834HCID 90455834, compound

Product 1

HCID 90461841HCID 90461841, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

A mixture of tert-butyl 3-(4-(2-(4-chloro-5-isopropyl-2-methoxyphenylamino)acetyl)piperazin-1-yl)azetidine-1-carboxylate (102 mg, 0.212 mmol) in HCl/MeOH (2.86 M, 5 mL) was stirred at RT for 1 h. The mixture was concentrated in vacuo to afford the crude product, the crude was dissolved in DMF (5 mL) at RT, acrylic acid (17 mg, 0.233 mmol), BOP (113 mg, 0.254 mmol) and DIEA (82 mg, 0.636 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=50:1) to afford the desired product (77 mg, 85% yield, 2 steps). ESI-MS m/z: 435.4[M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto afford the crude product
  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=50:1)

Sources & evidence

ORD record
ord-6667e73f199842f2bda586f58fc510b2
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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