1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86703536, compound

HRID 1849670Notes

Reaction equation

HRID 1849670 reaction equation
[CH:1]1([C:4]2[C:5]([O:14][CH2:15][C:16]34[CH2:25][CH:20]5[CH2:21][CH:22]([CH2:24][CH:18]([C:19]5([F:27])[F:26])[CH2:17]3)[CH2:23]4)=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]1.C(N=C=NCCCN(C)C)C.[N:39]1([S:43]([NH2:46])(=[O:45])=[O:44])[CH2:42][CH2:41][CH2:40]1>CN(C)C1C=CN=CC=1.ClCCl>[N:39]1([S:43]([NH:46][C:9](=[O:11])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[C:5]([O:14][CH2:15][C:16]34[CH2:17][CH:18]5[CH2:24][CH:22]([CH2:21][CH:20]([C:19]5([F:27])[F:26])[CH2:25]3)[CH2:23]4)=[CH:6][C:7]=2[F:13])(=[O:45])=[O:44])[CH2:42][CH2:41][CH2:40]1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 450805661-AzetidinesulfonamideHCID 86703535HCID 86703535, compound

Product 1

HCID 86703536HCID 86703536, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-cyclopropyl-4-((4,4-difluoroadamantan-1-yl)-methoxy)-2-fluorobenzoic acid (0.25 g, 0.66 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.29 g, 1.51 mmol) and 4-dimethylaminopyridine (0.19 g, 1.51 mmol) in anhydrous dichloromethane (10 mL) was added azetidine-1-sulfonamide (0.13 g, 0.99 mmol) at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The mixture was quenched with 1N 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 crude product was crystallized from ethyl acetate and hexanes and recrystallized from acetonitrile and water to afford the title compound as colorless solid (0.24 g, 73%): 1H NMR (300 MHz, DMSO-d6) δ 11.61 (s, 1H), 7.17 (d, J=8.3 Hz, 1H), 6.94 (d, J=12.9 Hz, 1H), 4.05 (t, J=7.7 Hz, 4H), 3.72 (s, 2H), 2.25-1.98 (m, 6H), 1.88-1.69 (m, 10H), 0.94-0.87 (m, 2H), 0.70-0.65 (m, 2H); MS (ES+) m/z 499.1 (M+1); MS (ES−) m/z 497.2 (M−1).

Workup

  1. customThe mixture was quenched with 1N 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 crude product was crystallized from ethyl acetate and hexanes
  8. customrecrystallized from acetonitrile and water

Sources & evidence

ORD record
ord-fa951cedc0c74465b376a40098a5dcff
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

Loading…