Diisopropylethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]cyclohexanecarboxamide

HRID 14317

Reaction equation

HRID 14317 reaction equation
[CH3:1][S:2]([CH2:5][CH:6]1[CH2:11][CH2:10][CH:9]([C:12]([OH:14])=O)[CH2:8][CH2:7]1)(=[O:4])=[O:3].[NH2:15][C@@H:16]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[C:33]([F:38])[CH:32]=1)[C@H:17]([OH:29])[CH2:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH3:28])[CH:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[F:37][C:35]1[CH:36]=[C:31]([CH:32]=[C:33]([F:38])[CH:34]=1)[CH2:30][C@H:16]([NH:15][C:12]([CH:9]1[CH2:8][CH2:7][CH:6]([CH2:5][S:2]([CH3:1])(=[O:3])=[O:4])[CH2:11][CH2:10]1)=[O:14])[C@H:17]([OH:29])[CH2:18][NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH3:28])[CH:22]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210859494-[(Methylsulfonyl)methyl]cyclohexanecarboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 21086881N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-[(methylsulfonyl)methyl]cyclohexanecarboxamideYield 22.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of acid from step 6 (100 mg, 0.5 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (190 mg, 0.5 mmol), and HATU (175 mg, 0.5 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (280 μL, 1.6 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between methylene chloride and water. The organic layer was washed with water, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, gradient 95:5 to 92:8 methylene chloride/methanol) provided the title compound (60 mg): mp 45-50° C.; ESI MS m/z 537 [M+H]+.

Workup

  1. customThe reaction mixture was partitioned between methylene chloride and water
  2. washThe organic layer was washed with water
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a crude oil
  7. customPurification by flash column chromatography (silica, gradient 95:5 to 92:8 methylene chloride/methanol)

Sources & evidence

ORD record
ord-2fe49f512ab1463185c38485c79ac3ab
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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