HCID 71062214, compound → HCID 71062193, compound

HRID 528818Notes

Reaction equation

HRID 528818 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][C:15]([S:19]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][C:28]([N:31]4[C:35]([CH3:36])=[C:34]([Cl:37])[C:33]([C:38]([N:40]([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:41][CH2:42][CH2:43][CH3:44])=[O:39])=[N:32]4)=[C:27]([C:49]([N:51]4[CH2:60][CH2:59][C:58]5[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=5)[CH2:52]4)=[O:50])[CH:26]=3)=[O:24])(=[O:21])=[O:20])=[CH:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1>CO.[Pd]>[CH2:45]([N:40]([CH2:41][CH2:42][CH2:43][CH3:44])[C:38]([C:33]1[C:34]([Cl:37])=[C:35]([CH3:36])[N:31]([C:28]2[CH:29]=[CH:30][C:25]([C:23](=[O:24])[NH:22][S:19]([C:15]3[CH:14]=[CH:13][C:12]4[C:17](=[CH:18][C:9]([OH:8])=[CH:10][CH:11]=4)[CH:16]=3)(=[O:21])=[O:20])=[CH:26][C:27]=2[C:49]([N:51]2[CH2:60][CH2:59][C:58]3[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=3)[CH2:52]2)=[O:50])[N:32]=1)=[O:39])[CH2:46][CH2:47][CH3:48]

Participants

4

Reactant 1

HCID 71062214HCID 71062214, compound

Product 1

HCID 71062193HCID 71062193, compoundYield 45.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of 1-(4-(7-(benzyloxy)naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (Example 18, 30 mg, 0.035 mmol) in MeOH (5.0 mL) was added 10% Pd/C (75 mg, 0.71 mmol). The flask was evacuated and purged with H2 from a balloon (2×), and the reaction mixture was then stirred overnight under an atmosphere of H2. The reaction mixture was diluted with CH2Cl2 and filtered through a pad of CELITE®, washing with CH2Cl2. The filtrate was concentrated in vacuo and purified by preparative HPLC to give the title compound (12 mg, 43%). 1H NMR (1:1 CD3OD:CDCl3, 1:1 mixture of amide rotamers) δ 8.37 (s, 1H), 8.17-8.13 (m, 1H), 8.05 (s, 1H), 7.93 (s, 1H), 7.80-7.76 (m, 2H), 7.70 (d, J=8.9 Hz, 1H), 7.34 (dd, J=8.5, 1.3 Hz, 1H), 7.23 (s, 1H), 7.17-7.05 (m, 4.5H), 6.83 (d, J=7.9 Hz, 0.5H), 4.66 (br s, 2H), 4.41 (s, 1H), 3.88 (br s, 1H), 3.51 (br s, 2H), 3.04-3.00 (m, 1H), 2.81-2.78 (m, 1H), 2.24 (s, 1.5H), 2.20 (s, 1.5H), 1.49-1.42 (m, 1H), 1.40-1.33 (m, 2H), 1.30-1.16 (m, 5H), 1.09-0.96 (m, 2H), 0.90-0.84 (m, 3H), 0.72 (t, J=7.4 Hz, 1.5H), 0.67 (t, J=7.4 Hz, 1.5H); MS (ESI+) m/z 756.2 (M+H)+.

Workup

  1. customThe flask was evacuated
  2. custompurged with H2 from a balloon (2×)
  3. additionThe reaction mixture was diluted with CH2Cl2
  4. filtrationfiltered through a pad of CELITE®
  5. washwashing with CH2Cl2
  6. concentrationThe filtrate was concentrated in vacuo
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-f6c3eb968b1648f683a866ffd06203f3
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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