Isobutyryl chloride → HCID 178454416, compound

HRID 1241522Notes

Reaction equation

HRID 1241522 reaction equation
[N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C@H:13]3[CH2:16][C@H:15]([CH2:17][N:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC1C=CC(S(O)(=O)=O)=CC=1.N1(CC2C=CC(C3CC(CN4CCNCC4)C3)=CC=2)CCCC1.C(N(C(C)C)CC)(C)C.[C:67](Cl)(=[O:71])[CH:68]([CH3:70])[CH3:69]>ClCCCl>[CH3:69][CH:68]([CH3:70])[C:67]([N:21]1[CH2:20][CH2:19][N:18]([CH2:17][C@H:15]2[CH2:16][C@H:13]([C:10]3[CH:9]=[CH:8][C:7]([CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)=[CH:12][CH:11]=3)[CH2:14]2)[CH2:23][CH2:22]1)=[O:71]

Participants

6

Reactant 4

HCID 62325Isobutyryl chlorideHCID 81531DiisopropylethylamineHCID 11426991(3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl]-piperazineHCID 178427641HCID 178427641, compound

Product 1

HCID 178454416HCID 178454416, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirring solution of Example 111, (3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl]-piperazine) (100 mg, 0.32 mmol) in 1,2-dichloroethane (4 mL) was added diisopropyl ethylamine (111 uL, 0.64 mmol) followed by the addition of isobutyryl chloride (50 uL, 0.48 mmol). After 15 min the reaction was quenched with 1N NaOH, extracted with dichloromethane. The combined organic layers were dried over MgSO4, filtered through a fritted funnel and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography, using a 12 g ISCO column, eluting with 4% MeOH/CH2Cl2 with 0.2% NH4OH. The product containing fractions were collected and concentrated to give the title compound (118 mg, 97% yield) as colorless oil. Rf=0.27 (10% MeOH/CH2Cl2 w/0.2% NH4OH); 500 MHz 1H NMR (CDCl3) δ 7.23 (d, J=8.3 Hz, 2H), 7.15 (d, J=8.3 Hz, 2H), 3.61–3.44 (m, 7H), 2.74 (septet, J=7.1 Hz, 1H), 2.56–2.45 (m, 7H), 2.42–2.34 (m, 4H), 2.28–2.20 (m, 2H), 2.17–2.09 (m, 2H), 1.79–1.70 (m, 4H), 1.08 (d, J=7.1 Hz, 6H); 125 MHz 13C NMR (CDCl3) δ 175.5, 145.1, 136.7, 129.1, 126.5, 64.3, 60.5, 54.3, 45.6, 41.8, 36.5, 33.4, 30.1, 29.0, 23.6, 19.6; LRMS m/z Calcd for C24H37N3O 383.6; obsd LRMS APCI (M+1) m/z 384.

Workup

  1. customAfter 15 min the reaction was quenched with 1N NaOH
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered through a fritted funnel
  5. concentrationconcentrated under reduced pressure
  6. customPurification of this material
  7. washeluting with 4% MeOH/CH2Cl2 with 0.2% NH4OH
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7ebe5cc8fdcf405d9593e59526eb9ff6
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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