Sodium 4-methyl-6-(2-methyl-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-olate → Ethyl 2-(4-Ethylpiperazin-1-yl)-2-(4-(4-methyl-6-(2-methyl-3-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)acetate

HRID 1363517Notes

Reaction equation

CN1C=C(C2C=CC=C(NC(C3SC4CCCCC=4C=3)=O)C=2C)N=C([O-])C1=O.[Na+].Br[C:31]1[N:36]=[C:35]([NH:37][C:38]2[CH:43]=[CH:42][C:41]([CH:44]([N:50]3[CH2:55][CH2:54][N:53]([CH2:56][CH3:57])[CH2:52][CH2:51]3)[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:40][CH:39]=2)[C:34](=[O:58])[N:33]([CH3:59])[CH:32]=1.[CH3:60][C:61]1[C:66](C2OC(C)(C)C(C)(C)O2)=[CH:65][CH:64]=[CH:63][C:62]=1[NH:76][C:77]([C:79]1[S:83][C:82]2[CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][C:81]=2[CH:80]=1)=[O:78]>>[CH2:56]([N:53]1[CH2:54][CH2:55][N:50]([CH:44]([C:41]2[CH:42]=[CH:43][C:38]([NH:37][C:35]3[C:34](=[O:58])[N:33]([CH3:59])[CH:32]=[C:31]([C:66]4[CH:65]=[CH:64][CH:63]=[C:62]([NH:76][C:77]([C:79]5[S:83][C:82]6[CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][C:81]=6[CH:80]=5)=[O:78])[C:61]=4[CH3:60])[N:36]=3)=[CH:39][CH:40]=2)[C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:51][CH2:52]1)[CH3:57]

Participants

Reactant 3

HCID 57625105Sodium 4-methyl-6-(2-methyl-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-olate

HCID 57625183ethyl 2-(4-(6-Bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)-2-(4-ethylpiperazin-1-yl)acetate

HCID 66941145N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide

Product 1

HCID 57625121Ethyl 2-(4-Ethylpiperazin-1-yl)-2-(4-(4-methyl-6-(2-methyl-3-(5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamido)phenyl)-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)acetateYield 73.2%

Procedure

Using the same procedure as described for the preparation of 10, the reaction of ethyl 2-(4-(6-Bromo-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino)phenyl)-2-(4-ethylpiperazin-1-yl)acetate (1.33 g) with N-(2-methyl-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-2-carboxamide (1.26 g) gave a 73% yield (1.39 g) of 45 as a tan foam: mp 168-170° C.; 1H NMR (300 MHz, CDCl3) δ 8.34 (s, 1H), 7.92 (d, 1H, J=7.8 Hz), 7.80 (d, 2H, J=8.7 Hz), 7.54 (s, 1H), 7.39 (d, 2H, J=8.7 Hz), 7.39 (s, 1H), 7.27 (t, 1H, J=8.1 Hz), 7.18 (dd, 1H, J=7.8, 1.2 Hz), 6.74 (s, 1H), 4.14 (m, 2H), 3.91 (s, 1H), 3.60 (s, 3H), 2.87 (t, 2H, J=5.7 Hz), 2.76 (t, 2H, J=5.7 Hz), 2.61 (br s, 8H), 2.32 (s, 3H), 1.88 (m, 2H), 1.77 (m, 4H), 1.17 (t, 3H, J=7.2 Hz), 1.05 (t, 3H, J=7.2 Hz); MS (ESI+) m/z 683 (M+H).

Sources & evidence

ORD record: ord-debe54a7c9984482aad26904b0cb39c9
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07884108B2

Reaction notes

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