Cyanomethylenetributylphosphorane → 3-[5-(4-Isopropyl-piperazine-1-carbonyl)-indol-1-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2113471Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([N:12]3[CH2:17][CH2:16][N:15]([CH:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH:30]([CH2:33]O)[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH:30]([CH2:33][N:1]2[C:9]3[C:4](=[CH:5][C:6]([C:10]([N:12]4[CH2:13][CH2:14][N:15]([CH:18]([CH3:20])[CH3:19])[CH2:16][CH2:17]4)=[O:11])=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 21.7 mg (0.08 mmol) (1H-indol-5-yl)-(4-isopropyl-piperazin-1-yl)-methanone (intermediate 1), 24.1 mg (0.12 mmol) 3-Hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (commercially available), 38.6 mg (0.16 mmol) cyanomethylenetri-n-butylphosphorane in 1.5 mL toluene was heated to 110° C. for an extended period of time. After evaporation the residue was purified by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile/water/NEt3. The combined product fractions were evaporated to yield 14.3 mg of the title compound. MS(m/e): 455.4 (MH+).

Workup

customAfter evaporation the residue
customwas purified by preparative HPLC on reversed phase
washeluting with a gradient
customformed from acetonitrile/water/NEt3
customThe combined product fractions were evaporated

Sources & evidence

ORD record: ord-4349b37cc7164b9bb4e7cb9e4e73f0b9
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07432255B2

Reaction notes

Loading…