Diisopropylethylamine → HCID 86709708, compound

HRID 2285413Notes

Reaction equation

HRID 2285413 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:26]([CH3:28])[CH3:27])[C:10]([NH:12][C@@H:13]([CH3:25])[C:14]([N:16]1[CH2:21][CH2:20][CH2:19][C@@H:18]([C:22](O)=[O:23])[NH:17]1)=[O:15])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:30][O:31][C:32](=[O:51])[C:33]([CH3:50])([CH3:49])/[CH:34]=[CH:35]/[C:36]1[CH:45]=[C:44]2[C:39]([CH:40]=[CH:41][C:42]([C@H:46]([NH2:48])[CH3:47])=[N:43]2)=[CH:38][CH:37]=1.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>[CH3:30][O:31][C:32](=[O:51])[C:33]([CH3:50])([CH3:49])/[CH:34]=[CH:35]/[C:36]1[CH:45]=[C:44]2[C:39]([CH:40]=[CH:41][C:42]([C@H:46]([NH:48][C:22]([C@@H:18]3[CH2:19][CH2:20][CH2:21][N:16]([C:14](=[O:15])[C@@H:13]([NH:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH:26]([CH3:28])[CH3:27])[CH3:25])[NH:17]3)=[O:23])[CH3:47])=[N:43]2)=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 866211442-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate MethanaminiumHCID 86709705HCID 86709705, compoundHCID 86709709HCID 86709709, compound

Product 1

HCID 86709708HCID 86709708, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A cooled (0° C.) solution of (S)-1-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid (696 mg, 1.74 mmol) and crude (E)-4-[2-((R)-1-amino-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoic acid methyl ester hydrochloride in acetonitrile (20 mL) was subsequently treated with N,N-diisopropylethylamine (1.52 mL, 8.71 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (861 mg, 2.26 mmol). After stirring at room temperature for 2 h, the volatiles were removed in vacuo. The residue was dissolved in ethyl acetate, and subsequently washed with saturated ammonium chloride solution and sodium hydrogen carbonate solution. The organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 100 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/acetone 1:0 to 1:1 to afford the title compound (868 mg, 73%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 0.82-0.97 (m, 6H), 1.36 (d, J=6.9 Hz, 3H), 1.45 (s, 9H), 1.48 (s, 6H), 1.61 (d, J=6.9 Hz, 3H), 1.66-1.76 (m, 2H), 1.83-2.12 (m, 3H), 2.78-2.92 (m, 1H), 3.52-3.61 (m, 1H), 3.74 (s, 3H), 3.82-3.95 (m, 1H), 4.25-4.35 (m, 1H), 5.23 (q, J=6.9 Hz, 1H), 5.36 (q, J=6.9 Hz, 1H), 6.36-6.51 (m, 2H), 7.51 (d, J=8.5 Hz, 1H), 7.73 (d, J=8.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 7.99 (s, 1H), 8.25 (d, J=8.5 Hz, 1H). LCMS (m/z) 681.4 [M+H], Tr=2.62 min.

Workup

  1. customthe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washsubsequently washed with saturated ammonium chloride solution and sodium hydrogen carbonate solution
  4. customthe volatiles were removed in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. washeluted with a continuous gradient of iso-hexanes/acetone 1:0 to 1:1

Sources & evidence

ORD record
ord-07cc383f6237472cb1ee9e5fc6303f38
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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