Diisopropylethylamine → HCID 86678379, compound

HRID 882628Notes

Reaction equation

HRID 882628 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][N:7]([CH3:64])[C@H:8]([C:12]([NH:14][C@H:15]([C:19]([N:21]([C@@H:23]([C@@H:60]([CH3:63])[CH2:61][CH3:62])[C@H:24]([O:58][CH3:59])[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C@H:33]([O:56][CH3:57])[C@@H:34]([CH3:55])[C:35]([NH:37][C@@:38]1([C:47]([N:49]2[CH2:54][CH2:53][CH2:52][CH2:51][O:50]2)=[O:48])[CH2:40][C@@H:39]1[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:36])=[O:27])[CH3:22])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH:9]([CH3:11])[CH3:10])([OH:3])=O.FC(F)(F)C(O)=O.[NH2:72][CH2:73][CH2:74][N:75]([CH3:88])[C:76](=[O:87])[CH2:77][CH2:78][CH2:79][N:80]1[C:84](=[O:85])[CH:83]=[CH:82][C:81]1=[O:86].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[O:86]=[C:81]1[CH:82]=[CH:83][C:84](=[O:85])[N:80]1[CH2:79][CH2:78][CH2:77][C:76]([N:75]([CH3:88])[CH2:74][CH2:73][NH:72][C:1](=[O:3])[CH2:4][CH2:5][CH2:6][N:7]([CH3:64])[C@H:8]([C:12]([NH:14][C@H:15]([C:19]([N:21]([C@@H:23]([C@@H:60]([CH3:63])[CH2:61][CH3:62])[C@H:24]([O:58][CH3:59])[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C@H:33]([O:56][CH3:57])[C@@H:34]([CH3:55])[C:35]([NH:37][C@@:38]1([C:47]([N:49]2[CH2:54][CH2:53][CH2:52][CH2:51][O:50]2)=[O:48])[CH2:40][C@@H:39]1[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:36])=[O:27])[CH3:22])=[O:20])[CH:16]([CH3:17])[CH3:18])=[O:13])[CH:9]([CH3:10])[CH3:11])=[O:87]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 70980590HCID 70980590, compoundHCID 86678351HCID 86678351, compound2×

Product 1

HCID 86678379HCID 86678379, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6 mg (7 μmol) of N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(1S,2R)-1-(1,2-oxazinan-2-ylcarbonyl)-2-phenylcyclopropyl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (Intermediate 61) were combined with 2.8 mg (8 μmol) of N-(2-aminoethyl)-4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-methylbutanamide trifluoroacetate, 10.1 mg (27 μmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and 5 μl of N,N-diisopropylethylamine in 2 ml of DMF and stirred at RT overnight. Then another 5 mg (23.5 μmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and 3 μl of N,N-diisopropylethylamine were added. After stirring at RT for a further 5 h, the solvent was removed under reduced pressure and the remaining residue was purified by means of preparative HPLC. The corresponding fractions were concentrated and, by lyophilization from dioxane, 1.3 mg (15% of theory) of the title compound were obtained.

Workup

  1. stirringAfter stirring at RT for a further 5 h
  2. customthe solvent was removed under reduced pressure
  3. customthe remaining residue was purified by means of preparative HPLC
  4. concentrationThe corresponding fractions were concentrated and, by lyophilization from dioxane, 1.3 mg (15% of theory) of the title compound
  5. customwere obtained

Sources & evidence

ORD record
ord-d2ae019776a34dd999f37d25d8edbb52
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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