(S)-4-((1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)morpholine → N,N-Dibutyl-4-chloro-5-methyl-1-(4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide

HRID 528944Notes

Reaction equation

HRID 528944 reaction equation
[Cl:1][C:2]1[C:3]([C:42](=[O:52])[N:43]([CH2:48][CH2:49][CH2:50][CH3:51])[CH2:44][CH2:45][CH2:46][CH3:47])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:41])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[C:25]([O:32][CH2:33][CH2:34][N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)[CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:9]=2[C:10](O)=[O:11])[C:6]=1[CH3:7].[CH2:53]1[C:62]2[C:57](=[CH:58][CH:59]=[CH:60][CH:61]=2)[CH2:56][C@@H:55]([CH2:63][N:64]2[CH2:69][CH2:68][O:67][CH2:66][CH2:65]2)[NH:54]1>>[CH2:48]([N:43]([CH2:44][CH2:45][CH2:46][CH3:47])[C:42]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:41])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[C:25]([O:32][CH2:33][CH2:34][N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)[CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:9]=2[C:10]([N:54]2[C@H:55]([CH2:63][N:64]3[CH2:69][CH2:68][O:67][CH2:66][CH2:65]3)[CH2:56][C:57]3[C:62](=[CH:61][CH:60]=[CH:59][CH:58]=3)[CH2:53]2)=[O:11])[N:4]=1)=[O:52])[CH2:49][CH2:50][CH3:51]

Participants

3

Reactant 2

HCID 28596890(S)-4-((1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)morpholine2×HCID 710622732-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)benzoic acid2×

Product 1

HCID 86718909N,N-Dibutyl-4-chloro-5-methyl-1-(4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)-2-((S)-3-(morpholinomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamideYield 72.3%

Procedure

Following a procedure analogous to that for the synthesis of Example 91, 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(8-(2-morpholinoethoxy) naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 183B, 15 mg, 0.020 mmol) and (S)-4-((1,2,3,4-tetrahydroisoquinolin-3-yl)methyl)morpholine (Intermediate 109, 18 mg, 0.080 mmol) were converted to the title compound (14 mg, 62%). 1H NMR (CD3OD, mixture of amide rotamers) δ 9.19-9.04 (m, 1H), 8.26-7.93 (m, 4H), 7.79-7.53 (m, 3H), 7.36-7.09 (m, 4H), 6.99 (d, J=7.7 Hz, 1H), 5.37-5.16 (m, 1H), 4.75-4.41 (m, 3.5H), 4.22-2.52 (m, 27.5H), 2.37-2.16 (m, 3H), 1.75-0.48 (m, 14H); MS(ESI+) m/z 968.3 (M+H)+.

Sources & evidence

ORD record
ord-2812755ded1d417d9fd43f9260235088
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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