2-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one → 5-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-one

HRID 1772153Notes

Reaction equation

HRID 1772153 reaction equation
C(C1SC2C(=O)N(C3C=CC=C(C4N=C(NC5C=CC(C6C(=O)NCCN6C)=CC=5)C(=O)N(C)C=4)C=3C)CC=2C=1)(C)(C)C.C([O:47][CH2:48][C:49]1[C:54](B2OC(C)(C)C(C)(C)O2)=[CH:53][CH:52]=[CH:51][C:50]=1[N:64]1[CH2:72][C:71]2[C:66](=[CH:67][CH:68]=[C:69]([N:73]([CH3:75])[CH3:74])[CH:70]=2)[C:65]1=[O:76])(=O)C.Br[C:78]1[CH:79]=[C:80]([NH:86][C:87]2[CH:92]=[CH:91][N:90]=[CH:89][N:88]=2)[C:81](=[O:85])[N:82]([CH3:84])[CH:83]=1>>[CH3:74][N:73]([CH3:75])[C:69]1[CH:70]=[C:71]2[C:66](=[CH:67][CH:68]=1)[C:65](=[O:76])[N:64]([C:50]1[CH:51]=[CH:52][CH:53]=[C:54]([C:78]3[CH:79]=[C:80]([NH:86][C:87]4[CH:92]=[CH:91][N:90]=[CH:89][N:88]=4)[C:81](=[O:85])[N:82]([CH3:84])[CH:83]=3)[C:49]=1[CH2:48][OH:47])[CH2:72]2

Participants

4

Reactant 3

HCID 569284422-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-oneHCID 580440945-bromo-1-methyl-3-(pyrimidin-4-ylamino)pyridin-2(1H)-oneHCID 866998722-(5-(Dimethylamino)-1-oxoisoindolin-2-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl Acetate

Product 1

HCID 569288605-(Dimethylamino)-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(pyrimidin-4-ylamino)-1,6-dihydropyridin-3-yl)phenyl)isoindolin-1-oneYield 33.6%

Procedure

Using the same general procedure as described for the preparation of 104, reaction of 123e (400 mg, 0.890 mmol) with 107a (207 mg, 0.740 mmol) followed by a hydrolysis gave a 28% yield (120 mg) of 124 as a white solid: mp 206-208° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.73 (d, 1H, J=2.0 Hz), 8.65 (s, 1H), 8.30 (d, 1H, J=6.0 Hz), 7.57 (d, 1H, J=8.5 Hz), 7.55 (d, 1H, J=2.5 Hz), 7.49 (t, 1H, J=2.5 Hz), 7.43 (dd, 1H, J=8.0, 1.5 Hz), 7.37 (dd, 1H, J=8.0, 1.5 Hz), 7.31 (dd, 1H, J=6.0, 1.5 Hz), 6.88-6.85 (m, 2H), 4.94 (t, 1H, J=4.5 Hz), 4.86 (s, 2H), 4.32 (d, 2H, J=4.5 Hz), 3.61 (s, 3H), 3.04 (s, 6H); MS (ESI+) m/z 483.2 (M+H).

Sources & evidence

ORD record
ord-0e4cdfa5867142b89a41ebef002bad46
Source dataset
uspto-grants-2016_02
Patent number
US09249123B2

Reaction notes

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