Hydrochloric Acid → 1-(2-((S)-3-(Aminomethyl)-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 528943Notes

Reaction equation

HRID 528943 reaction equation
[N:1]([CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16])=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+].Cl>C1COCC1.O>[NH2:1][CH2:4][C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][N:6]1[C:15]([C:17]1[CH:22]=[C:21]([C:23](=[O:47])[NH:24][S:25]([C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[C:31]([O:38][CH2:39][CH2:40][N:41]4[CH2:42][CH2:43][O:44][CH2:45][CH2:46]4)[CH:32]=[CH:33][CH:34]=3)[CH:29]=2)(=[O:27])=[O:26])[CH:20]=[CH:19][C:18]=1[N:48]1[C:52]([CH3:53])=[C:51]([Cl:54])[C:50]([C:55]([N:57]([CH2:62][CH2:63][CH2:64][CH3:65])[CH2:58][CH2:59][CH2:60][CH3:61])=[O:56])=[N:49]1)=[O:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 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-carboxamide

Product 1

HCID 867189081-(2-((S)-3-(Aminomethyl)-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 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (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 (45 mg, 0.049 mmol) and PPh3 (38 mg, 0.15 mmol) in THF (4.0 mL) and water (0.4 mL) was added 1N aq. NaOH solution (0.2 mL, 0.20 mmol). The resulting reaction mixture was heated at 50° C. for 3 h and then acidified (pH=1) with 1N aq. HCl solution. The solvent was removed in vacuo, and the residue was purified by preparative HPLC to give the title compound (33 mg, 72%) as a white solid. 1H NMR (CD3OD, mixture of amide rotamers) δ 9.16 (s, 1H), 8.29-7.88 (m, 4H), 7.83-7.58 (m, 3H), 7.40-7.08 (m, 4H), 6.99 (br s, 1H), 5.04 (br s, 0.5H), 4.76-4.41 (m, 4H), 4.27-2.66 (m, 18.5H), 2.42-2.20 (m, 3H), 1.64-0.72 (m, 13H), 0.60 (br s, 1H); MS(ESI+) m/z 898.1 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3069e063c18d4a4a9576286fa8da8894
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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