1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(morpholinosulfonyl)-benzamide

HRID 1427867Notes

Reaction equation

HRID 1427867 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([Cl:22])=[CH:20][C:16]([C:17](O)=[O:18])=[C:15]([F:23])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(N=C=NCCCN(C)C)C.[N:35]1([S:41]([NH2:44])(=[O:43])=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>CN(C)C1C=CN=CC=1.ClCCl>[C:1]12([CH2:11][O:12][C:13]3[C:21]([Cl:22])=[CH:20][C:16]([C:17]([NH:44][S:41]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)(=[O:43])=[O:42])=[O:18])=[C:15]([F:23])[CH:14]=3)[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 2767394-MorpholinesulfonamideHCID 867028594-(Adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoic acid

Product 1

HCID 867028894-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(morpholinosulfonyl)-benzamideYield 20.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoic acid (0.17 g, 0.50 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.22 g, 1.15 mmol) and 4-dimethylaminopyridine (0.14 g, 1.15 mmol) in anhydrous dichloromethane (10 mL) was added morpholine-4-sulfonamide (0.17 g, 1.0 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 h. The mixture was quenched with hydrochloride acid (1N, 30 mL) followed by extraction with ethyl acetate (100 mL). The organic layer was washed with water (30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the residue was purified by silica gel column chromatography using 10-60% gradient ethyl acetate (containing 0.2% acetic acid) in hexanes to afford the title compound as an off-white solid (0.05 g, 20%): 1H NMR (300 MHz, DMSO-d6) δ 7.88 (s, 1H), 6.88 (s, 1H), 4.06 (d, J=6.8 Hz, 2H), 3.39 (s, 3H), 2.50-2.42 (m, 1H), 2.12-2.05 (m, 1H), 1.98-1.94 (m, 1H), 1.90-1.68 (m, 4H), 1.50-1.41 (m, 2H), 1.22 (s, 3H), 0.87 (s, 3H); MS (ES−) m/z 397.2, 399.2 (M−1); MS (ES+) m/z 399.1, 401.1 (M+1);

Workup

  1. customThe mixture was quenched with hydrochloride acid (1N, 30 mL)
  2. extractionfollowed by extraction with ethyl acetate (100 mL)
  3. washThe organic layer was washed with water (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0297c3bffea841e5b198f16ebe2a8c9c
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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