1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 72188014, compound

HRID 515185Notes

Reaction equation

HRID 515185 reaction equation
[CH:1]1([C:4]2[CH:12]=[C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=[C:9]([CH3:19])[C:5]=2[C:6]([OH:8])=O)[CH2:3][CH2:2]1.C(N=C=NCCCN(C)C)C.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.[NH2:50][CH2:51][CH2:52][C@@H:53]([OH:58])[C:54]([CH3:57])([CH3:56])[CH3:55]>ClCCl.O>[CH:1]1([C:4]2[CH:12]=[C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=[C:9]([CH3:19])[C:5]=2[C:6]([NH:50][CH2:51][CH2:52][C@@H:53]([OH:58])[C:54]([CH3:57])([CH3:56])[CH3:55])=[O:8])[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 55283766HCID 55283766, compoundHCID 86699750HCID 86699750, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 72188014HCID 72188014, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-cyclopropyl-6-methyl-4-morpholin-4-yl-benzoic acid (synthesized according to the methods described in sections a) to f)) (0.34 g, 1.3 mmol) in dichloromethane (10 ml) are added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.30 g, 1.56 mmol), hydroxybenzotriazole (0.21 g, 1.56 mmol) and diisopropylethylamine (0.65 ml, 3.9 mmol) at 0° C. and stirred for 15 min before the addition of (3R)-1-amino-4,4-dimethyl-pentan-3-ol (synthesized according to the methods described in sections g) to k)) (0.28 g, 1.69 mmol). The resulting mixture is stirred at room temperature for 16 h. Water (20 ml) is added to the mixture and extracted with dichloromethane (3×20 ml). The combined organic layers are washed with 10% sodium hydrogen carbonate solution (30 ml), brine (30 ml), dried over sodium sulfate and concentrated in vacuo. The crude product is purified by column chromatography (silica gel, 55% ethyl acetate/dichloromethane) yielding 2-cyclopropyl-N-[(3R)-3-hydroxy-4,4-dimethyl-pentyl]-6-methyl-4-morpholin-4-yl-benzamide (example 28) (0.19 g, 0.51 mmol, 39%). [M+H]+ 375.3. [α]D25=+30.0° (c 1.0, methanol).

Workup

  1. customsynthesized
  2. extractionextracted with dichloromethane (3×20 ml)
  3. washThe combined organic layers are washed with 10% sodium hydrogen carbonate solution (30 ml), brine (30 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by column chromatography (silica gel, 55% ethyl acetate/dichloromethane)

Sources & evidence

ORD record
ord-42c889cc7c46431fb0eba456610c77e9
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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