Diisopropylethylamine → HCID 71543395, compound

HRID 709353Notes

Reaction equation

HRID 709353 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:37]=[C:38]1[C@@H:44]([NH:45][C:46](=[O:49])[O:47][CH3:48])[CH2:43][CH2:42][C:41](=[O:50])[N:40]2[CH2:51][CH2:52][CH2:53][C@@H:54]([C:55]3[NH:56][C:57]([C:60]4[CH:65]=[CH:64][C:63]([C:66]5[CH:75]=[N:74][C:73]6[C:68](=[CH:69][CH:70]=[C:71]([C:76]7[NH:80][C:79]([C@@H:81]8[CH2:85][CH2:84][CH2:83][NH:82]8)=[N:78][CH:77]=7)[CH:72]=6)[N:67]=5)=[CH:62][CH:61]=4)=[CH:58][N:59]=3)[N:39]12.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O.O>[CH3:48][O:47][C:46](=[O:49])[NH:45][C@H:44]1[CH2:43][CH2:42][C:41](=[O:50])[N:40]2[CH2:51][CH2:52][CH2:53][C@@H:54]([C:55]3[NH:56][C:57]([C:60]4[CH:65]=[CH:64][C:63]([C:66]5[CH:75]=[N:74][C:73]6[C:68](=[CH:69][CH:70]=[C:71]([C:76]7[NH:80][C:79]([C@@H:81]8[CH2:85][CH2:84][CH2:83][N:82]8[C:7](=[O:9])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:10]([CH3:12])[CH3:11])=[N:78][CH:77]=7)[CH:72]=6)[N:67]=5)=[CH:62][CH:61]=4)=[CH:58][N:59]=3)[N:39]2[C:38]1=[O:37]

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 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 90399380HCID 90399380, compound

Product 1

HCID 71543395HCID 71543395, compoundYield 57.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

In a 10 mL pear-shaped flask, (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (8.35 mg, 47.7 μmol) was combined with DMF (1 ml) (1 ml) to give a colorless solution. HATU (14.5 mg, 38.1 μmol) was added and stirred for 10 min. methyl (4S,7S)-6,10-dioxo-4-(5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)quinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)octahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate (21 mg, 31.8 μmol) in 2 ml of DMF and DIPEA (20.5 mg, 27.8 μl, 159 μmol) were added and stirred at room temperature for 1 hr. It was diluted with brine and H2O (10 ml each) and the precipitate was filtered, washed with H2O and hexane, dried on high vacuum at 46° C. to afford ((4S,7S)-4-{5-[4-(6-{2-[(S)-1-((S)-2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-quinoxalin-2-yl)-phenyl]-1H-imidazol-2-yl}-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl)-carbamic acid methyl ester as a light brownish solid (15 mg, 53.1%). ESI-LRMS m/e calcd for C42H47N11O7, [M+] 817. found 818 [M+H]. 1H NMR (DMSO-d6) δ: 12.34 (br. s., 1H), 12.02 (br. s., 1H), 9.29-9.68 (m, 1H), 8.21-8.52 (m, 4H), 7.71-8.11 (m, 5H), 7.15-7.60 (m, 2H), 5.83 (br. s., 1H), 5.12 (br. s., 1H), 4.46 (br. s., 3H), 4.09 (br. s., 1H), 3.85 (br. s., 3H), 3.56 (d, J=7.5 Hz, 6H), 2.90 (br. s., 3H), 1.56-2.39 (m, 8H), 0.76-1.06 (m, 6H).

Workup

  1. customto give a colorless solution
  2. additionwere added
  3. filtrationthe precipitate was filtered
  4. washwashed with H2O and hexane
  5. customdried on high vacuum at 46° C.

Sources & evidence

ORD record
ord-d937791896764c96bcb52a5b28ab5f0f
Source dataset
uspto-grants-2015_11
Patent number
US09180193B2

Reaction notes

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