Diisopropylethylamine → HCID 88532377, compound

HRID 1427756Notes

Reaction equation

HRID 1427756 reaction equation
[CH3:1][O:2][C@H:3]([C@@H:9]([CH3:28])[C@@H:10]([O:26][CH3:27])/[CH:11]=[CH:12]/[Sn:13]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:15][CH2:16][CH3:17])[C@@H:4](C)[C:5](O)=O.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[I:62][C:63]1[CH:64]=[C:65]([CH:109]=[CH:110][CH:111]=1)[CH2:66][O:67][C:68]([C@@H:70]1[CH2:75][CH2:74][CH2:73][N:72]([C:76](=[O:108])[C@@H:77]([NH:93][C:94](=[O:107])[C@@H:95]([NH:99][C:100](OC(C)(C)C)=[O:101])[CH:96]([CH3:98])[CH3:97])[CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([O:85][Si:86]([C:89]([CH3:92])([CH3:91])[CH3:90])([CH3:88])[CH3:87])[CH:80]=2)[NH:71]1)=[O:69]>CN(C=O)C>[I:62][C:63]1[CH:64]=[C:65]([CH:109]=[CH:110][CH:111]=1)[CH2:66][O:67][C:68]([C@@H:70]1[CH2:75][CH2:74][CH2:73][N:72]([C:76](=[O:108])[C@@H:77]([NH:93][C:94](=[O:107])[C@@H:95]([NH:99][C:100](=[O:101])[C@H:4]([CH3:5])[C@H:3]([O:2][CH3:1])[C@@H:9]([CH3:28])[C@@H:10]([O:26][CH3:27])/[CH:11]=[CH:12]/[Sn:13]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:18][CH2:19][CH2:20][CH3:21])[CH:96]([CH3:98])[CH3:97])[CH2:78][C:79]2[CH:84]=[CH:83][CH:82]=[C:81]([O:85][Si:86]([C:89]([CH3:90])([CH3:91])[CH3:92])([CH3:88])[CH3:87])[CH:80]=2)[NH:71]1)=[O:69]

Participants

6

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 67957649HCID 67957649, compoundHCID 86675860HCID 86675860, compound

Product 1

HCID 88532377HCID 88532377, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To (E)-(2R,3R,4R,5R)-3,5-Dimethoxy-2,4-dimethyl-7-tributylstannanyl-hept-6-enoic acid (5b) (85 mg, 0.17 mmol) in anhydrous DMF (1.1 ml) at 0° C. and under an atmosphere of nitrogen was added Diisopropylethylamine (0.12 ml, 0.67 mmol), followed by HATU (64 mg, 0.17 mmol). The reaction was stirred for 1.5 hours after which a solution of (S)-1-{(S)-2-((S)-2-tert-Butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid 3-iodo-benzyl ester (134 mg, 0.19 mmol) in anhydrous DMF (1.1 ml) was added. The reaction was warmed to room temperature, stirred for 16 hours and quenched with pH7 buffer. The reaction was extracted with dichloromethane (3×), the organics dried through a hydrophobic frit and concentrated in vacuo. The product was purified by flash chromatography (SiO2, iHex/EtOAc, 2:1) to afford 5c100 mg (57%) as a viscous oil. 1H NMR (300 MHz, CDCl3) δ 7.52 (m, 2H), 7.14 (d, J=7.6 Hz, 1H), 6.96 (t, J=7.6 Hz, 1H), 6.87 (t, J=7.6 Hz, 1H), 6.63 (m, 1H), 6.51 (m, 3H), 6.31 (t, J=8.8 Hz, 1H), 6.08 (d, J=8.5 Hz, 1H), 5.96 (d, J=19 Hz, 1H), 5.56 (m, 1H), 5.50 (dd, J=19 Hz, 7.9 Hz, 1H), 4.89 (m, 2H), 4.12 (m, 2H), 3.68 (d, J=9.4 Hz, 1H), 3.34 (d, J=10.5 Hz, 1H), 3.22 (s, 3H), 3.14 (t, J=8.8 Hz, 1H), 3.07 (s, 3H), 2.83-2.60 (m, 3H), 2.30 (m, 1H), 2.20 (m, 1H), 1.97 (m, 1H), 1.71-1.47 (m, 4H), 1.33 (m, 6H), 1.15 (m, 6H), 0.89 (d, J=7.0 Hz, 3H), 0.82-0.69 (m, 30H), 0.60 (d, J=7.0 Hz, 3H), 0.006 (m, 6H). LCMS (m/z) 1211.48 [M+H], Tr=7.29 min.

Workup

  1. additionwas added
  2. customquenched with pH7 buffer
  3. extractionThe reaction was extracted with dichloromethane (3×)
  4. customthe organics dried through a hydrophobic frit
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by flash chromatography (SiO2, iHex/EtOAc, 2:1)
  7. customto afford 5c100 mg (57%) as a viscous oil
  8. customLCMS (m/z) 1211.48 [M+H], Tr=7.29 min.

Sources & evidence

ORD record
ord-d818358f98d04f47a342e3d3b3cd5334
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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