1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-((2S,3R)-3-hydroxy-1-phenyl-4-(3-(trifluoromethyl)benzylamino)butan-2-yl)-3-methyl-5-((R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl)benzamide

HRID 2071189Notes

Reaction equation

HRID 2071189 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[O:12])[CH:10]=1)[C:5](O)=[O:6].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:45][C@@H:46]([CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[C@H:47]([OH:61])[CH2:48][NH:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([C:57]([F:60])([F:59])[F:58])[CH:52]=1.CCN(C(C)C)C(C)C.O1C2C=CC=CC=2C=C1CNC(=O)OC(C)(C)C>C(Cl)Cl.C(OCC)(=O)C>[OH:61][C@H:47]([CH2:48][NH:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([C:57]([F:58])([F:59])[F:60])[CH:52]=1)[C@@H:46]([NH:45][C:5](=[O:6])[C:4]1[CH:8]=[C:9]([C:11]([N:13]2[CH2:17][CH2:16][CH2:15][C@@H:14]2[C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[O:12])[CH:10]=[C:2]([CH3:1])[CH:3]=1)[CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57487214(2R,3S)-3-amino-4-phenyl-1-(3-(trifluoromethyl)benzylamino)butan-2-olHCID 57512780(R)-3-methyl-5-(2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl)benzoic acidHCID 68671575Tert-butyl benzofuran-2-ylmethylcarbamate

Product 1

HCID 25254345N-((2S,3R)-3-hydroxy-1-phenyl-4-(3-(trifluoromethyl)benzylamino)butan-2-yl)-3-methyl-5-((R)-2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl)benzamideYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To (R)-3-methyl-5-(2-(4-methylthiazol-2-yl)pyrrolidine-1-carbonyl)benzoic acid (330 mg, 1 mmol) in CH2Cl2 at rt, EDCI (269 mg, 1.4 mmol) and HOBT (162 mg, 1.20 mmol) were added and stirred at rt for 20 min. In a separate flask (2R,3S)-3-amino-4-phenyl-1-(3-(trifluoromethyl)benzylamino)butan-2-ol was taken in CH2Cl2 and treated with DIPEA (2 ml). After 20 min, flask containing acid was cooled to 0° C. and the amine was added to it. Reaction mixture was stirred at rt for 16 h. Then reaction mixture was diluted with ethyl acetate, washed with sodium bicarbonate, water, brine and dried. Crude residue was purified by column chromatography to yield 60% of desired product.

Workup

  1. waitAfter 20 min
  2. additionflask containing acid
  3. temperaturewas cooled to 0° C.
  4. customReaction mixture
  5. stirringwas stirred at rt for 16 h
  6. customThen reaction mixture
  7. washwashed with sodium bicarbonate, water, brine
  8. customdried
  9. customCrude residue was purified by column chromatography

Sources & evidence

ORD record
ord-c06fbac3dfa04c56bbc9ad0305d8e559
Source dataset
uspto-grants-2012_10
Patent number
US08299267B2

Reaction notes

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