Diisopropylethylamine → HCID 86685777, compound

HRID 74822Notes

Reaction equation

HRID 74822 reaction equation
[O:1]=[C:2]1[CH:6]=[CH:5][C:4](=[O:7])[N:3]1[CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[CH3:55][NH:56][C:57]([CH3:105])([C:59]([NH:61][C@H:62]([C:66]([N:68]([C@@H:70]([C@@H:101]([CH3:104])[CH2:102][CH3:103])[C@H:71]([O:99][CH3:100])[CH2:72][C:73]([N:75]1[CH2:79][CH2:78][CH2:77][C@H:76]1[C@H:80]([O:97][CH3:98])[C@@H:81]([CH3:96])[C:82]([NH:84][C@H:85]([C:93]([OH:95])=[O:94])[CH2:86][C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1)=[O:83])=[O:74])[CH3:69])=[O:67])[CH:63]([CH3:65])[CH3:64])=[O:60])[CH3:58]>ClCCl.CS(C)=O.CN(C=O)C>[O:7]=[C:4]1[CH:5]=[CH:6][C:2](=[O:1])[N:3]1[CH2:8][CH2:9][CH2:10][CH2:11][C:12]([N:56]([CH3:55])[C:57]([CH3:105])([C:59]([NH:61][C@H:62]([C:66]([N:68]([C@@H:70]([C@@H:101]([CH3:104])[CH2:102][CH3:103])[C@H:71]([O:99][CH3:100])[CH2:72][C:73]([N:75]1[CH2:79][CH2:78][CH2:77][C@H:76]1[C@H:80]([O:97][CH3:98])[C@@H:81]([CH3:96])[C:82]([NH:84][C@H:85]([C:93]([OH:95])=[O:94])[CH2:86][C:87]1[CH:92]=[CH:91][CH:90]=[CH:89][CH:88]=1)=[O:83])=[O:74])[CH3:69])=[O:67])[CH:63]([CH3:64])[CH3:65])=[O:60])[CH3:58])=[O:14]

Participants

8

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 232738725-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)pentanoic acidHCID 86685778N,2-dimethylalanyl-N-{(1S,2R)-4-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-2-methoxy-1-[(1S)-1-methylpropyl]-4-oxobutyl}-N-methyl-L-valinamide-trifluoroacetic acid salt

Product 1

HCID 86685777HCID 86685777, compoundYield 3.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of 5-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)pentanoic acid (12 mg, 0.061 mM) in 0.4 mL of dichloromethane, and 0.1 mL of DMF, HATU (23.2 mg, 0.061 mM) was added followed by Hunig's base (0.033 mL, 0.188 mM). The reaction was allowed to stir for 5 minutes before #115 (39 mg, 0.047 mM) was added as a solution in 0.4 mL of dichloromethane, and 0.1 mL of DMF. The reaction was allowed to stir at room temperature for 3 hours and 15 minutes before being quenched through the addition of water containing a small amount of TFA. Reaction was then reduced down. Crude material was dissolved with DMSO and purified by reverse phase chromatography (Method J). The appropriate fractions were concentrated then (Genevac). Material was then further purified by reverse phase chromatography (Method K) with the appropriate fractions being concentrated (Genevac). Material was then transferred to a small vial using dichloromethane and methanol before being reduced down (Genevac) to afford mv#115 (1.4 mg, 3.3%) oil/solid mix. HPLC (Protocol A at 45° C.): m/z 897.5 [M+H+], retention time=9.149 minutes (purity >97%).

Workup

  1. custombefore being quenched through the addition of water containing a small amount of TFA
  2. customReaction
  3. custompurified by reverse phase chromatography (Method J)
  4. concentrationThe appropriate fractions were concentrated
  5. customMaterial was then further purified by reverse phase chromatography (Method K) with the appropriate fractions
  6. concentrationbeing concentrated (Genevac)

Sources & evidence

ORD record
ord-4816497456ca46f9a2fe9bd4f1a522b9
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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