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1-Hydroxybenzotriazole → 1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamide

HRID 348963
Notes
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Reaction equation

HRID 348963 reaction equation
[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][C@@H:58]([CH2:72][C:73]1[CH:78]=[C:77]([F:79])[CH:76]=[C:75]([F:80])[CH:74]=1)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=1>C(Cl)Cl.C(N(CC)CC)C>[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([N:17]([CH3:22])[S:18]([CH3:21])(=[O:20])=[O:19])[CH:10]=[C:11]([C:14]([NH:57][C@@H:58]([CH2:72][C:73]3[CH:74]=[C:75]([F:80])[CH:76]=[C:77]([F:79])[CH:78]=3)[C@H:59]([OH:71])[CH2:60][NH:61][CH2:62][C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([CH2:69][CH3:70])[CH:64]=3)=[O:16])[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210851741-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 57508185
1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamide
Yield 53.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 1-Butyl-4-[methyl (methylsulfonyl) amino]-1H-indole-6-carboxylic acid (0.2 g) in methylene chloride (15 mL) was added triethylamine (0.156 g), HOBT (0.105 g), and HATU (0.293 g). The mixture was stirred at 39° C. for 10 minutes at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.293 g) was added. The mixture was stirred at 40° C. for 4 h then poured into methylene chloride (50 mL), washed with water followed by brine then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Column chromatography on silica gel (100 mL) using 5% methanol in methylene chloride as eluent to give 0.21 g of the title compound: MS (ESI+) for C34H42F2N4O4S1 m/z 640.8 (M+H).

Workup

  1. additionwas added
  2. washwashed with water
  3. dry with materialthen dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-12bd69be504243cebab75aa6c1124857
Source dataset
uspto-grants-2007_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07176242B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes