Lithium Hydroxide → (R)-2-(3-(5-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HRID 1026424Notes

Reaction equation

C[C@H]1N(C)CCN(C2C=CC(NC3C(=O)N(C)C=C(C4C(CO)=C(N5CCN6C7CCCCC=7C=C6C5=O)C=C(F)C=4)C=3)=NC=2)C1.C([O:50][CH2:51][C:52]1[C:57]([N:58]2[CH2:70][CH2:69][N:61]3[C:62]4[CH2:63][CH2:64][CH2:65][CH2:66][C:67]=4[CH:68]=[C:60]3[C:59]2=[O:71])=[CH:56][C:55]([F:72])=[CH:54][C:53]=1[C:73]1[CH:78]=[C:77]([NH:79][C:80]2[CH:85]=[CH:84][C:83]([N:86]3[CH2:91][CH2:90][N:89]([CH3:92])[CH2:88][C@H:87]3[CH3:93])=[CH:82][N:81]=2)[C:76](=[O:94])[N:75]([CH3:95])[CH:74]=1)(=O)C.[OH-].[Li+]>>[CH3:93][C@@H:87]1[CH2:88][N:89]([CH3:92])[CH2:90][CH2:91][N:86]1[C:83]1[CH:84]=[CH:85][C:80]([NH:79][C:77]2[C:76](=[O:94])[N:75]([CH3:95])[CH:74]=[C:73]([C:53]3[C:52]([CH2:51][OH:50])=[C:57]([N:58]4[CH2:70][CH2:69][N:61]5[C:62]6[CH2:63][CH2:64][CH2:65][CH2:66][C:67]=6[CH:68]=[C:60]5[C:59]4=[O:71])[CH:56]=[C:55]([F:72])[CH:54]=3)[CH:78]=2)=[N:81][CH:82]=1

Participants

Reactant 3

HCID 3939Lithium Hydroxide

HCID 71526524(R)-2-(3-(5-(5-(3,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)-phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-one

HCID 86683721(R)-2-(5-(5-(2,4-Dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Product 1

HCID 71526687(R)-2-(3-(5-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-5-fluoro-2-(hydroxymethyl)phenyl)-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-1(2H)-oneYield 48.6%

Procedure

Following the procedures as described for compound 108, hydrolysis of 109f (337 mg, 0.5 mmol) with lithium hydroxide gave 109 as a yellow solid (152 mg, 48%). LCMS: (M+H)+ 626. 1H NMR (500 MHz, DMSO) δ 8.57 (t, J=2.5, 1H), 8.39 (s, 1H), 7.83 (d, J=3.0, 1H), 7.31-7.36 (m, 3H), 7.23 (d, J=9.0, 1H), 7.17-7.20 (m, 1H), 6.53 (s, 1H), 4.86-4.88 (m, 1H), 4.32 (d, J=4.5, 2H), 4.09-4.20 (m, 3H), 3.87-3.91 (m, 1H), 3.66 (s, 1H), 3.59 (s, 3H), 3.04-3.08 (m, 1H), 2.90-2.94 (m, 1H), 2.57-2.65 (m, 3H), 2.47 (t, J=5.5, 2H), 2.35-2.42 (m, 2H), 2.19-2.21 (m, 1H), 2.18 (s, 3H), 1.79 (t, J=6.0, 2H), 1.66-1.69 (m, 2H), 0.91 (d, J=6.0, 3H)

Sources & evidence

ORD record: ord-853dcc60002348fa8dc600cc9122b22a
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729072B2

Reaction notes

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