2-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)benzoic acid → (S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

HRID 528942Notes

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

Participants

Reactant 2

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

HCID 86718892(S)-3-(Azidomethyl)-1,2,3,4-tetrahydroisoquinoline2×

Product 1

HCID 86718907(S)-1-(2-(3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-4-(8-(2-morpholinoethoxy)naphthalen-2-ylsulfonylcarbamoyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamideYield 73.7%

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, 50 mg, 0.066 mmol) and (S)-3-(azidomethyl)-1,2,3,4-tetrahydroisoquinoline (Intermediate 92A, 37 mg, 0.20 mmol) were converted to the title compound (45 mg, 73%). 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 9.23-9.11 (m, 1H), 8.21 (d, J=1.9 Hz, 0.5H), 8.13-7.93 (m, 3.5H), 7.76-7.58 (m, 3H), 7.32-7.06 (m, 4.5H), 6.93 (d, J=7.2 Hz, 0.5H), 5.28 (d, J=18.3 Hz, 0.5H), 4.98 (br s, 0.5H), 4.73-4.62 (m, 2H), 4.59-3.21 (m, 15.5H), 3.18-2.69 (m, 3.5H), 2.58 (d, J=16.1 Hz, 0.5H), 2.48-2.40 (m, 0.5H), 2.34-2.21 (m, 3H), 1.55-0.82 (m, 1H), 0.78-0.70 (m, 2H), 0.69-0.55 (m, 1H); MS(ESI+) m/z 924.3 (M+H)+.

Sources & evidence

ORD record: ord-3ab64b06cd6149319fb7752e8e96331b
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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