Morpholine → HCID 71062310, compound

HRID 528813Notes

Reaction equation

HRID 528813 reaction equation
[Cl:1][C:2]1[C:3]([C:45](=[O:55])[N:46]([CH2:51][CH2:52][CH2:53][CH3:54])[CH2:47][CH2:48][CH2:49][CH3:50])=[N:4][N:5]([C:8]2[CH:32]=[CH:31][C:11]([C:12]([NH:14][S:15]([C:18]3[CH:27]=[C:26]4[C:21]([CH:22]=[CH:23][C:24]([C:28](O)=[O:29])=[CH:25]4)=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[O:13])=[CH:10][C:9]=2[C:33]([N:35]2[CH2:44][CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:36]2)=[O:34])[C:6]=1[CH3:7].[NH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1>>[CH2:47]([N:46]([CH2:51][CH2:52][CH2:53][CH3:54])[C:45]([C:3]1[C:2]([Cl:1])=[C:6]([CH3:7])[N:5]([C:8]2[CH:32]=[CH:31][C:11]([C:12](=[O:13])[NH:14][S:15]([C:18]3[CH:19]=[CH:20][C:21]4[C:26](=[CH:25][C:24]([C:28]([N:56]5[CH2:61][CH2:60][O:59][CH2:58][CH2:57]5)=[O:29])=[CH:23][CH:22]=4)[CH:27]=3)(=[O:16])=[O:17])=[CH:10][C:9]=2[C:33]([N:35]2[CH2:44][CH2:43][C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH2:36]2)=[O:34])[N:4]=1)=[O:55])[CH2:48][CH2:49][CH3:50]

Participants

3

Reactant 2

HCID 8083MorpholineHCID 71062246HCID 71062246, compound2×

Product 1

HCID 71062310HCID 71062310, compoundYield 23.4%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 12B of Example 12, 7-(N-(4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoyl)sulfamoyl)-2-naphthoic acid (Intermediate 46A 12 mg, 0.015 mmol) and morpholine (4 mg, 0.046 mmol) were converted to the title compound (3 mg, 20%). 1H NMR (1:1 CD3OD:CDCl3, 2:1 mixture of amide rotamers) δ 8.67 (s, 1H), 8.21 (d, J=8.3 Hz, 1H), 8.14 (dd, J=8.7, 1.5 Hz, 1H), 8.11 (d, J=1.7 Hz, 1H), 8.06 (s, 1H), 7.98 (t, J=7.6 Hz, 2H), 7.60 (d, J=8.3 Hz, 1H), 7.44-7.42 (m, 1H), 7.19-7.09 (m, 3.5H), 6.89 (d, J=7.2 Hz, 0.5H), 4.83 (br s, 1H), 4.50 (s, 1H), 4.36 (br s, 1H), 3.79 (br s, 4H), 3.68 (br s, 3H), 3.54 (br s, 3H), 3.45 (s, 1H), 3.00 (br s, 1.5H), 2.83 (br s, 1.5H), 2.29 (s, 2H), 2.24 (s, 1H), 1.50-1.44 (m, 1H), 1.40-1.35 (m, 2H), 1.32-1.16 (m, 4H), 1.12-0.99 (m, 2H), 0.92-0.86 (m, 3H), 0.75 (t, J=7.4 Hz, 2H), 0.68 (t, J=7.4 Hz, 1H); MS(ESI+) m/z 853.3 (M+H)+.

Sources & evidence

ORD record
ord-89e4993300304580bf0b7ee3e275bb1f
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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