Diisopropylethylamine → (2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acid

HRID 1713946Notes

Reaction equation

HRID 1713946 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([OH:18])=O)=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:24])[CH3:23])=[O:21])[C:8]=2[C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:63][C:64]1([C:69]([NH:71][C:72]2[CH:77]=[CH:76][C:75](/[CH:78]=[CH:79]/[C:80]([O:82]CC)=[O:81])=[CH:74][CH:73]=2)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]1>CN(C=O)C.C1COCC1.CO>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([NH:63][C:64]4([C:69]([NH:71][C:72]5[CH:73]=[CH:74][C:75](/[CH:78]=[CH:79]/[C:80]([OH:82])=[O:81])=[CH:76][CH:77]=5)=[O:70])[CH2:68][CH2:67][CH2:66][CH2:65]4)=[O:18])=[CH:13][CH:14]=3)[N:9]([CH2:19][C:20]([N:22]([CH3:23])[CH3:24])=[O:21])[C:8]=2[C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

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 114635753-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acidHCID 58745796Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

Product 1

HCID 11621612(2E)-3-[4-({[1-({[3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indol-6-yl]carbonyl}amino)cyclopentyl]carbonyl}amino)phenyl]acrylic acidYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution (0.04 M) of 3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-2-(1,3-oxazol-5-yl)-1H-indole-6-carboxylic acid (from Step 6) in DMF was treated with DIPEA (3 eq.), HATU (2 eq.) and ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate (from Example 1, Step 7, 1.1 eq.). The solution was stirred at 25° C. for 12 h and then evaporated in vacuo. The residual material was purified by chromatography on silica gel (PE:EtOAc, 8:2, then EtOAc:PE 9:1). The product fractions were evaporated and the material obtained was then dissolved in THF/MeOH (1:1). The resulting solution was treated with LiOH monohydrate (3 eq.) and stirred at RT overnight. The product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min). After lyophilisation the product was obtained as a colourless amorphous solid (98%).

Workup

  1. customevaporated in vacuo
  2. customThe residual material was purified by chromatography on silica gel (PE
  3. customThe product fractions were evaporated
  4. customthe material obtained
  5. stirringstirred at RT overnight
  6. customThe product was isolated by preparative HPLC (stationary phase: Waters Xterra C18 19×150 mm, 5 micron; flow 20 mL/min)

Sources & evidence

ORD record
ord-880b96217574481d82e86a3f04e1ab36
Source dataset
uspto-grants-2010_09
Patent number
US07795250B2

Reaction notes

Loading…