Diisopropylethylamine → HCID 86708885, compound

HRID 1895785Notes

Reaction equation

HRID 1895785 reaction equation
[C:1]([Si:5]([CH3:46])([CH3:45])[O:6][C:7]1[CH:8]=[C:9]([CH2:13][C@H:14]([NH:26][C:27](=[O:44])[C@@H:28]([NH:32][C:33](=[O:43])[C@H:34]([CH3:42])[C@H:35]([O:40][CH3:41])[CH2:36][CH2:37][CH:38]=[CH2:39])[CH:29]([CH3:31])[CH3:30])[C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([C:23](O)=[O:24])[NH:18]2)=[O:16])[CH:10]=[CH:11][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[CH:48]([C:50]1[CH:51]=[C:52]([C@H:56]([NH2:58])[CH3:57])[CH:53]=[CH:54][CH:55]=1)=[CH2:49].C(N(CC)C(C)C)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F>C(#N)C.O.C(OCC)(=O)C>[CH:48]([C:50]1[CH:51]=[C:52]([C@H:56]([NH:58][C:23]([C@@H:19]2[CH2:20][CH2:21][CH2:22][N:17]([C:15](=[O:16])[C@@H:14]([NH:26][C:27](=[O:44])[C@@H:28]([NH:32][C:33](=[O:43])[C@H:34]([CH3:42])[C@H:35]([O:40][CH3:41])[CH2:36][CH2:37][CH:38]=[CH2:39])[CH:29]([CH3:30])[CH3:31])[CH2:13][C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:45])[CH3:46])[CH:8]=3)[NH:18]2)=[O:24])[CH3:57])[CH:53]=[CH:54][CH:55]=1)=[CH2:49]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 67957637HCID 67957637, compoundHCID 67957726HCID 67957726, compoundHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

Product 1

HCID 86708885HCID 86708885, compoundYield 58.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (S)-1-{(S)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-[(S)-2-((2R,3R)-3-methoxy-2-methyl-hept-6-enoylamino)-3-methyl-butyrylamino]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (480 mg, 0.72 mmol), (R)-1-(3-vinylphenyl)ethylamine hydrochloride (159 mg, 0.86 mmol) and N,N-diisopropylethylamine (372 mg, 0.5 mL, 2.88 mmol) in acetonitrile (20 mL) was stirred at room temperature under nitrogen. 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (380 mg, 1 mmol) was added and the reaction mixture was stirred at room temperature for 24 hours. Ethyl acetate and water were added. The aqueous layer was separated and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:1 to neat ethyl acetate to afford the title compound (331 mg, 58%) as a white foam. 1H NMR (300 MHz, CD3CN) δ0.20 (s, 6H), 0.81 (d, J=6.9 Hz, 3H), 0.82 (d, J=6.7 Hz, 3H), 0.99 (m, 9H), 1.03 (d, J=6.9 Hz, 3H), 1.40 (d, J=7.1 Hz, 3H), 1.45-2.20 (m, 7H), 2.50-2.70 (m, 2H), 2.75-2.85 (m, 1H), 2.95-3.15 (m, 2H), 3.30 (s, 3H), 3.30-3.35 (m, 1H), 3.95-4.15 (m, 2H), 4.25-4.35 (m, 1H), 4.93-5.10 (m, 4H), 5.25 (dd, J=10.9, 0.9 Hz, 1H), 5.28 (dd, J=10.9, 0.9 Hz, 1H), 5.49-5.58 (m, 1H), 5.81 (dd, J=17.6, 0.9 Hz, 1H), 5.83 (dd, J=17.6, 0.9 Hz, 1H), 6.54-6.61 (m, 1H), 6.70-6.84 (m, 5H), 7.10 (t, J=7.6 Hz, 1H), 7.24-7.43 (m, 6H). LCMS (m/z) 790 [M+H], Tr=5.91 min.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 24 hours
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-fde044924d0442a4af87ba4aef367c82
Source dataset
uspto-grants-2013_08
Patent number
US08513184B2

Reaction notes

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