Diisopropylethylamine → (E)-Hept-2-enoic acid [(S)-2-(3,5-difluorophenyl)-1-((3S,7S,13S,16S,19S)-13,16,17-trimethyl-2,6,12,15,18-pentaoxo-5-oxa-1,11,14,17-tetraazatricyclo[17.3.0.07,11]docos-3-ylcarbamoyl)-ethyl]-amide

HRID 751767

Reaction equation

HRID 751767 reaction equation
FC(F)(F)C([O-])=O.[F:8][C:9]1[CH:10]=[C:11]([CH2:16][C@H:17]([NH3+:51])[C:18](=[O:50])[NH:19][C@H:20]2[CH2:41][O:40][C:39](=[O:42])[C@H:38]3[N:34]([CH2:35][CH2:36][CH2:37]3)[C:33](=[O:43])[C@H:32]([CH3:44])[NH:31][C:30](=[O:45])[C@H:29]([CH3:46])[N:28]([CH3:47])[C:27](=[O:48])[C@H:26]3[N:22]([CH2:23][CH2:24][CH2:25]3)[C:21]2=[O:49])[CH:12]=[C:13]([F:15])[CH:14]=1.[C:52](O)(=[O:59])/[CH:53]=[CH:54]/[CH2:55][CH2:56][CH2:57][CH3:58].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>ClCCl>[F:8][C:9]1[CH:10]=[C:11]([CH2:16][C@H:17]([NH:51][C:52](=[O:59])/[CH:53]=[CH:54]/[CH2:55][CH2:56][CH2:57][CH3:58])[C:18](=[O:50])[NH:19][C@H:20]2[CH2:41][O:40][C:39](=[O:42])[C@H:38]3[N:34]([CH2:35][CH2:36][CH2:37]3)[C:33](=[O:43])[C@H:32]([CH3:44])[NH:31][C:30](=[O:45])[C@H:29]([CH3:46])[N:28]([CH3:47])[C:27](=[O:48])[C@H:26]3[N:22]([CH2:23][CH2:24][CH2:25]3)[C:21]2=[O:49])[CH:12]=[C:13]([F:15])[CH:14]=1

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 52827092-Heptenoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86598030(S)-2-(3,5-Difluorophenyl)-1-((3S,7S,13S,16S,19S)-13,16,17-trimethyl-2,6,12,15,18-pentaoxo-5-oxa-1,11,14,17-tetraaza-tricyclo[17.3.0.07,11]docos-3-ylcarbamoyl)-ethylammonium 2,2,2-trifluoroacetate

Product 1

HCID 11422732(E)-Hept-2-enoic acid [(S)-2-(3,5-difluorophenyl)-1-((3S,7S,13S,16S,19S)-13,16,17-trimethyl-2,6,12,15,18-pentaoxo-5-oxa-1,11,14,17-tetraazatricyclo[17.3.0.07,11]docos-3-ylcarbamoyl)-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2.89 g (2.75 mmol) of the compound from example 13A and 458.8 mg (3.58 mmol) of trans-2-heptenoic acid are introduced into dichloromethane (20 ml), cooled to 0° C., then treated with 2.09 g (5.51 mmol) of HATU and 462.7 mg (3.58 mmol) of ethyldiisopropylamine. The solution is stirred at 0° C. for 30 min, then a further 925.3 mg (7.16 mmol) of ethyldiisopropylamine are added, and it is stirred at room temperature for 18 h. The reaction solution is evaporated, and the residue is taken up using ethyl acetate and washed with aq. citric acid, aq. sodium hydrogencarbonate solution and sat. aq. sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness. The residue is chromatographed on silica gel using ethyl acetate/cyclohexane 1/2. 1.51 g (56% of th.) of the product are obtained.

Workup

  1. stirringit is stirred at room temperature for 18 h
  2. customThe reaction solution is evaporated
  3. washwashed with aq. citric acid, aq. sodium hydrogencarbonate solution and sat. aq. sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue is chromatographed on silica gel
  8. custom1.51 g (56% of th.) of the product are obtained

Sources & evidence

ORD record
ord-6ec2906cbcb043bd9e21265ab3d5278a
Source dataset
uspto-grants-2008_07
Patent number
US07405201B2

Linked notes

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