2-[8-(Benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-{3-[2-fluoro-4-(4-methyl-piperazin-1-yl)-phenoxy]-propyl}-thiazole-4-carboxylic acid → 6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(2-fluoro-4-(4-methylpiperazin-1-yl)phenoxy)propyl)picolinic acid

HRID 1518396Notes

Reaction equation

HRID 1518396 reaction equation
S1[C:5]2C=CC=C[C:4]=2N=C1NC(C1C=CC=C2C=1CN(C1SC(CCCI)=C(C(OCC)=O)N=1)CC2)=O.[S:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]=[C:38]1[NH:46][C:47]([C:49]1[CH:50]=[CH:51][CH:52]=[C:53]2[C:58]=1[CH2:57][N:56]([C:59]1S[C:61]([CH2:67][CH2:68][CH2:69][O:70][C:71]3[CH:76]=[CH:75][C:74]([N:77]4[CH2:82][CH2:81][N:80]([CH3:83])[CH2:79][CH2:78]4)=[CH:73][C:72]=3[F:84])=[C:62]([C:64]([OH:66])=[O:65])[N:63]=1)[CH2:55][CH2:54]2)=[O:48].S1C2C=CC=CC=2N=C1NC(C1C=CC=C2C=1CN(C1N=C(C(OC(C)(C)C)=O)C(CCCI)=CC=1)CC2)=O>>[S:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]=[C:38]1[NH:46][C:47]([C:49]1[CH:50]=[CH:51][CH:52]=[C:53]2[C:58]=1[CH2:57][N:56]([C:59]1[N:63]=[C:62]([C:64]([OH:66])=[O:65])[C:61]([CH2:67][CH2:68][CH2:69][O:70][C:71]3[CH:76]=[CH:75][C:74]([N:77]4[CH2:78][CH2:79][N:80]([CH3:83])[CH2:81][CH2:82]4)=[CH:73][C:72]=3[F:84])=[CH:5][CH:4]=1)[CH2:55][CH2:54]2)=[O:48]

Participants

4

Reactant 3

HCID 468368652-[8-(Benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-{3-[2-fluoro-4-(4-methyl-piperazin-1-yl)-phenoxy]-propyl}-thiazole-4-carboxylic acidHCID 59447467ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylateHCID 59447593tert-butyl 6-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-iodopropyl)picolinate

Product 1

HCID 594476756-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(2-fluoro-4-(4-methylpiperazin-1-yl)phenoxy)propyl)picolinic acid

Procedure

The title compound 101 was prepared using the same procedure described in step 2 of Example 54 by replacing compound 54A and compound 2C with compound 93 and compound 96D, respectively: 1H NMR (400 MHz, DMSO-D6) δ ppm 12.80 (1H, s), 9.61 (1H, s), 8.03 (1H, d), 7.79 (1H, d), 7.60 (1H, d), 7.55 (1H, d), 7.44-7.51 (1H, m), 7.39-7.43 (1H, m), 7.33-7.38 (2H, m), 7.02 (1H, t), 6.90-6.98 (2H, m), 6.70 (1H, dd), 4.93 (2H, s), 3.93 (2H, t), 3.86 (2H, t), 3.67-3.75 (2H, m), 3.26-3.37 (2H, m), 3.06-3.20 (2H, m), 2.99 (2H, t), 2.76-2.93 (7H, m), 1.86-1.99 (2H, m); LCMS (APCI) m/e 681 (M+H).

Sources & evidence

ORD record
ord-7937158cfddd43f08a648c3caa27ce83
Source dataset
uspto-grants-2012_07
Patent number
US08232273B2

Reaction notes

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