1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 86703565, compound

HRID 1849694Notes

Reaction equation

HRID 1849694 reaction equation
[CH:1]1([C:4]2[C:5]([O:14][CH2:15][C:16]3([CH3:26])[CH2:25][CH2:24][C:19]4([C:21]([F:23])([F:22])[CH2:20]4)[CH2:18][CH2:17]3)=[CH:6][C:7]([F:13])=[C:8]([CH:12]=2)[C:9](O)=[O:10])[CH2:3][CH2:2]1.Cl.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>ClCCl.CN(C)C1C=CN=CC=1>[N:39]1([S:43]([NH:46][C:9](=[O:10])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[C:5]([O:14][CH2:15][C:16]3([CH3:26])[CH2:17][CH2:18][C:19]4([C:21]([F:22])([F:23])[CH2:20]4)[CH2:24][CH2:25]3)=[CH:6][C:7]=2[F:13])(=[O:45])=[O:44])[CH2:42][CH2:41][CH2:40]1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 450805661-AzetidinesulfonamideHCID 86703564HCID 86703564, compound

Product 1

HCID 86703565HCID 86703565, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-cyclopropyl-4-((1,1-difluoro-6-methylspiro[2.5]-octan-6-yl)methoxy)-2-fluorobenzoic acid (0.039 g, 0.106 mmol) in dichloromethane (3 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide hydrochloride (0.031 g, 0.159 mmol) and 4-dimethylaminopyridine (0.030 g, 0.244 mmol). The reaction was stirred at ambient temperature for 10 minutes, azetidine-1-sulfonamide (0.023 g, 0.17 mmol) was added and the stirring was continued at ambient temperature for 17 hours. The reaction was concentrated, diluted with ethyl acetate (10 mL) and washed with 5% aqueous hydrochloric acid solution (5 mL). The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (0% to 30% ethyl acetate in hexanes) afforded the title compound (0.043 g, 83%) as a white solid [mixture of cis/trans diastereomers]: 1H NMR (300 MHz, CDCl3) [second diastereomer peaks in italics] δ 8.64 (d, J=16.5 Hz, 1H), 7.63 (d, J=9.1 Hz, 1H), 6.58 [6.56](d, J=14.0 Hz, 1H), 4.24 (t, J=7.7 Hz, 4H), 3.77 [3.72](s, 2H), 2.32-2.19 (m, 2H), 2.06-1.94 (m, 1H), 1.82-1.37 (m, 6H), 1.29-1.10 (m, 5H), 1.08-0.83 (m, 4H), 0.70-0.60 (m, 2H); MS (ES−) m/z 485.3 (M−1).

Workup

  1. waitthe stirring was continued at ambient temperature for 17 hours
  2. concentrationThe reaction was concentrated
  3. additiondiluted with ethyl acetate (10 mL)
  4. washwashed with 5% aqueous hydrochloric acid solution (5 mL)
  5. customThe organic layer was separated
  6. washwashed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by column chromatography (0% to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0178f566ff6a4d99a1d901e333cddcbd
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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