Acetic Acid → (1R,2S)-2-(4-chlorophenyl)-1'-(2-(4-isopropylpiperazin-1-yl)ethyl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805327Notes

Reaction equation

HRID 1805327 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH:20]=O)[C:11]3=[O:22])[CH2:9]2)=[CH:4][CH:3]=1.[CH:23]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:25])[CH3:24].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][N:29]4[CH2:30][CH2:31][N:26]([CH:23]([CH3:25])[CH3:24])[CH2:27][CH2:28]4)[C:11]3=[O:22])[CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 780131-IsopropylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 58305328(1S,2R)-2-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)acetaldehyde

Product 1

HCID 58305276(1R,2S)-2-(4-chlorophenyl)-1'-(2-(4-isopropylpiperazin-1-yl)ethyl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 82.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R,2S) and (1S,2R)-2-(2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)acetaldehyde (0.1 mmol), (1-Isopropyl)piperazine (0.15 mmol) and acetic acid (catalytic amount) in DCM (2 ml) was stirred for 20 minutes at room temperature. The mixture was cooled to 0° C. and NaBH(OAc)3 (2 mmol) was added carefully. The mixture was warmed to room temperature and stirred for 14 hours at room temperature. The mixture was concentrated under reduced pressure and dissolved in DMF. Purification by preparative HPLC gave the title product as colorless oil (35 mg). LC/MS m/e calcd. for C25H30ClN3O: 423, observed (M+H)+: 424.1 1HNMR (400 MHz, MeOD-d4) δppm 1.37 (d, J=6.57 Hz, 6 H) 2.18 (dd, J=8.46, 5.94 Hz, 2 H) 2.46-2.64 (m, 1H) 2.85 (d, J=3.54 Hz, 2 H) 3.22 (s, 2 H) 3.50 (d, J=6.57 Hz, 2 H) 3.90-4.27 (m, 2 H) 6.09 (d, J=7.58 Hz, 1H) 6.76 (s, 1 H) 7.10 (d, J=7.83 Hz, 1 H) 7.16-7.25 (m, 3 H) 7.33 (d, J=8.59 Hz, 2 H).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. temperatureThe mixture was warmed to room temperature
  3. stirringstirred for 14 hours at room temperature
  4. concentrationThe mixture was concentrated under reduced pressure
  5. dissolutiondissolved in DMF
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-ee205c3da47c43fbb058c4a10cc602fb
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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