Cyclopropanecarboxylic acid → HCID 25221338, compound

HRID 1642499Notes

Reaction equation

HRID 1642499 reaction equation
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@@H:22]4[C@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]4)[CH2:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:24]1([C:27](O)=[O:28])[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH:24]1([C:27]([N:5]2[CH2:4][CH2:3][C:2]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]4[C@@H:22]5[C@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]5)[CH2:16][C:15]4=[O:23])[CH2:10][CH2:9]3)([CH3:1])[CH2:7][CH2:6]2)=[O:28])[CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57619825HCID 57619825, compound

Product 1

HCID 25221338HCID 25221338, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (3aR,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-indol-2-one (70 mg, 0.22 mmol) in DMF (3 mL) was added with cyclopropane carboxylic acid (18.86 mg, 0.22 mmol) and diisopropylethyl amine (0.046 mL, 0.26 mmol) at room temperature. After 5-10 minutes HATU (83 mg, 0.22 mmol) was added and the mixture stirred at room temperature over night. The solvent was removed in vacuo, the residue dissolved in dichloromethane (60 mL) and washed with 1N NaOH (7 mL) and brine and concentrated in vacuo. The residue was purified by preparative LC/MS (high pH) to provide the title compound (58 mg, 69%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.54-0.74 (m, 2H), 0.77-0.95 (m, 2H), 0.84 (s, 3H), 1.01-1.44 (m, 6H), 1.45-1.84 (m, 11H), 2.01-2.15 (m, 2H), 2.19-2.40 (m, 2H), 2.73-3.06 (m, 3H), 3.17-3.32 (m, 1H), 3.37 (s, 1H), 3.44-3.68 (m, 2H), 3.69-3.80 (m, 1H), 3.81-3.97 (m, 1H). MS (M+1): 388.3.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in dichloromethane (60 mL)
  3. washwashed with 1N NaOH (7 mL) and brine
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative LC/MS (high pH)

Sources & evidence

ORD record
ord-f00e7d1852f84548967268ad1d245f0f
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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