1-Methylpiperazine → 8-[(2R)-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)]-6-(4-methylpiperazine-1-carbonyl)-2-morpholino-4H-chromen-4-one

HRID 41196Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[C:14]2[CH:15]=[C:16]([C:31]([OH:33])=O)[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:20][C:19]3=[O:30])[CH:5]=[C:6]([F:8])[CH:7]=1.CCN(C(C)C)C(C)C.[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(Cl)Cl>[F:8][C:6]1[CH:5]=[C:4]([N:9]2[CH2:13][CH2:12][CH2:11][C@@H:10]2[C:14]2[CH:15]=[C:16]([C:31]([N:47]3[CH2:48][CH2:49][N:44]([CH3:43])[CH2:45][CH2:46]3)=[O:33])[CH:17]=[C:18]3[C:23]=2[O:22][C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:20][C:19]3=[O:30])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

Conditions

Temperature: 25 °C

Procedure

8-[(2R)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acid (see Example 1.03b for preparation, 97 mg, 0.21 mmol), DIPEA (0.185 mL, 1.06 mmol) and 1-methylpiperazine (0.047 mL, 0.43 mmol) were mixed at room temperature in DCM (3 mL). N-propylphosphonic acid anhydride, cyclic trimer (50 wt % solution in EtAc) (0.633 mL, 1.08 mmol) was then added and the reaction mixture was stirred at 25° C. for 1 hour. The reaction mixture was purified by preparative HPLC to afford 8-[(2R)-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)]-6-(4-methylpiperazine-1-carbonyl)-2-morpholino-4H-chromen-4-one (67 mg, 59%) as a white foam.

Workup

customThe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record: ord-1dffb34fb800496c966cb485c5e11185
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530470B2

Reaction notes

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