Triethylamine → 3-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-1H-indole-5-carboxamide

HRID 349006Notes

Reaction equation

HRID 349006 reaction equation
[CH2:1]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[NH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:48][C@@H:49]([CH2:63][C:64]1[CH:69]=[C:68]([F:70])[CH:67]=[C:66]([F:71])[CH:65]=1)[C@H:50]([OH:62])[CH2:51][NH:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[C:56]([CH2:60][CH3:61])[CH:55]=1>C(Cl)Cl>[CH2:1]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([NH:48][C@@H:49]([CH2:63][C:64]3[CH:65]=[C:66]([F:71])[CH:67]=[C:68]([F:70])[CH:69]=3)[C@H:50]([OH:62])[CH2:51][NH:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([CH2:60][CH3:61])[CH:55]=3)=[O:16])[CH:12]=2)[NH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210857253-butyl-1H-indole-5-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 575082133-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-1H-indole-5-carboxamideYield 69.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 3-Butyl-1H-indole-5-carboxylic acid (0.145 g) in methylene chloride (15 mL) was added triethylamine (0.068 g), and HATU (0.255 g). The mixture was stirred at room temperature for 15 minutes at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.224 g) was added. The mixture was stirred at room temperature for 72 h then poured into methylene chloride (50 mL), washed with water then saturated sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated under vacuum. Column chromatography on silica gel (100 mL) using 5% methanol in methylene chloride with 0.15% HOAc as eluent to give 0.247 g of the title compound: MS (ESI+) for C32H37F2N3O2 m/z 534.3 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with water
  3. dry with materialsaturated sodium bicarbonate, dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-fe292adcaa1648f894531c1d066eb8fc
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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