1,2-Dichloroethane → N1-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-ethynyl-N3,N3-dipropylisophthalamide

HRID 14029Notes

Reaction equation

HRID 14029 reaction equation
[NH2:1][C:2]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([C:13]([N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])=[O:14])[CH:12]=1)[C:7](O)=O)=[O:3].[F:22][C:23]([F:28])([F:27])[C:24](O)=O.N[C@@H:30]([CH2:44][C:45]1[CH:50]=[C:49](F)[CH:48]=[C:47](F)[CH:46]=1)[C@H:31]([OH:43])[CH2:32][NH:33][CH2:34][C:35]1[CH:40]=C[CH:38]=[C:37](OC)[CH:36]=1.[CH:53]1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>C(Cl)Cl.O>[CH2:44]([C@H:30]([NH:1][C:2](=[O:3])[C:4]1[CH:5]=[C:6]([C:7]#[CH:53])[CH:10]=[C:11]([C:13]([N:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])=[O:14])[CH:12]=1)[C@H:31]([OH:43])[CH2:32][NH:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:24]([C:23]([F:28])([F:27])[F:22])[CH:40]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 223948913-Carbamoyl-5-dipropylcarbamoyl-benzoic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 86585857N1-((1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl)-5-ethynyl-N3,N3-dipropylisophthalamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-[(dipropylamino)carbonyl]-5-ethynylbenzoic acid (IX, 231 mg, 0.8 mmol), (2R,3S)-3-amino-4-phenyl-1-{[3-(trifluoromethyl)benzyl]amino}-2-butanol dihydrochloride (VIII, Step 2, 493.5 mg, 1.2 mmol) HOBt (162 mg, 1.2 mmol), and diisopropylethylamine (832 Micro Liter, 4.8 mmol) is stirred in methylene chloride (4 mL) for 15 minutes EDC (206 mg, 1.2 mmol) is added and the reaction mixture is stirred overnight. The reaction mixture is diluted with water, and extracted with methylene chloride (3×25 mL). The organic phase is washed with hydrochloric acid (1N, 25 mL), saturated sodium bicarbonate (25 mL), saline dried over sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (silica, 100% ethyl acetate to methanol/chloroform, 1/9) gives title compound, IR (ATR): 3302, 2963, 2932 and 1615 cm−1; MS (m/z) [M+H]+=549.

Workup

  1. additionis added
  2. extractionextracted with methylene chloride (3×25 mL)
  3. washThe organic phase is washed with hydrochloric acid (1N, 25 mL), saturated sodium bicarbonate (25 mL), saline
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica, 100% ethyl acetate to methanol/chloroform, 1/9)

Sources & evidence

ORD record
ord-69ed6418af02485e8263f17ebb8930d3
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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