Diisopropylethylamine → 4-Isobutoxy-1h-indole-2-carboxylic acid {1-[2-(3-fluoro-piperidin-1-yl)-ethyl]-piperidin-4-yl}-amide

HRID 1929221Notes

Reaction equation

[N:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([NH:15][C:16]([C:18]3[NH:19][C:20]4[C:25]([CH:26]=3)=[C:24]([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:23]=[CH:22][CH:21]=4)=[O:17])[CH2:11][CH2:10]2)[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1.Cl.[F:33]C1CCCNC1.CCN(C(C)C)C(C)C.[I-].C(C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#N>C(#N)CC.CCOC(C)=O>[F:33][CH:5]1[CH2:4][CH2:3][CH2:2][N:1]([CH2:7][CH2:8][N:9]2[CH2:10][CH2:11][CH:12]([NH:15][C:16]([C:18]3[NH:19][C:20]4[C:25]([CH:26]=3)=[C:24]([O:27][CH2:28][CH:29]([CH3:31])[CH3:30])[CH:23]=[CH:22][CH:21]=4)=[O:17])[CH2:13][CH2:14]2)[CH2:6]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a suspension of 190 (see example 150) (100 mg, 0.28 mmol), 3-fluoropiperidine hydrochloride (43 mg, 0.208 mmol) and DIEA (0.189 ml, 1.12 mmol) in 0.5 ml of propionitrile is added cyanomethyl-triphenyl phosphonium iodide (81 mg, 0.336 mmol). The mixture is heated at 90° C. for 14 hours. The resulting solution is then diluted with EtOAc (20 ml) and washed twice with saturated sodium bicarbonate, dried over sodium sulfate and evaporated. The crude product is further purified by preparative HPLC.

Workup

washwashed twice with saturated sodium bicarbonate
dry with materialdried over sodium sulfate
customevaporated
customThe crude product is further purified by preparative HPLC

Sources & evidence

ORD record: ord-65dcf333f78c4dd0b08b47696bc29889
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183366B2

Reaction notes

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