1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(adamantan-1-ylmethoxy)-N-((3-cyanoazetidin-1-yl)sulfonyl)-5-cyclopropyl-2-fluorobenzamide

HRID 1849671Notes

Reaction equation

HRID 1849671 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:16]([C:17]([OH:19])=O)=[C:15]([F:25])[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.[C:37]([CH:39]1[CH2:42][N:41]([S:43]([NH2:46])(=[O:45])=[O:44])[CH2:40]1)#[N:38]>CN(C)C1C=CN=CC=1.ClCCl>[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:23][CH2:24]4)=[CH:20][C:16]([C:17]([NH:46][S:43]([N:41]4[CH2:42][CH:39]([C:37]#[N:38])[CH2:40]4)(=[O:45])=[O:44])=[O:19])=[C:15]([F:25])[CH:14]=3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 867028614-(Adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acidHCID 867035383-Cyanoazetidine-1-sulfonamide

Product 1

HCID 867035374-(adamantan-1-ylmethoxy)-N-((3-cyanoazetidin-1-yl)sulfonyl)-5-cyclopropyl-2-fluorobenzamideYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoic acid (0.20 g, 0.60 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.26 g, 1.38 mmol) and 4-dimethylaminopyridine (0.17 g, 1.38 mmol) in anhydrous dichloromethane (10 mL) was added 3-cyanoazetidine-1-sulfonamide (0.22 g, 1.38 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The mixture was quenched with 1 M aqueous hydrochloride acid (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% ethyl acetate (containing 2% acetic acid) in hexanes as an elute to afford the title compound as colorless solid (0.23 g, 79%): 1H NMR (300 MHz, DMSO-d6) δ 11.88 (s, 1H), 7.18 (d, J=8.3 Hz, 1H), 6.95 (d, J=13.0 Hz, 1H), 4.35-4.22 (m, 4H), 3.84-3.74 (m, 1H), 3.65 (s, 2H), 2.09-1.99 (m, 4H), 1.75-1.67 (m, 12H), 0.95-0.87 (m, 2H), 0.70-0.65 (m, 2H); MS (ES+) m/z 488.2 (M+1); MS (ES−) m/z 486.3 (M−1).

Workup

  1. customThe mixture was quenched with 1 M aqueous hydrochloride acid (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
  8. washan elute

Sources & evidence

ORD record
ord-7ba5aec6f2ab40e49492bba6231c7c69
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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