Diisopropylethylamine → HCID 67048095, compound

HRID 409975Notes

Reaction equation

HRID 409975 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][NH:31][CH2:32][CH2:33][O:34][CH3:35])=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:36])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.C([NH:44][C@H:45]([C:49](O)=[O:50])[CH:46]([CH3:48])[CH3:47])(OC(C)(C)C)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.ClCCl.FC(F)(F)C(O)=O>[NH2:44][C@H:45]([CH:46]([CH3:48])[CH3:47])[C:49]([N:31]([CH2:30][C:27]1[CH:26]=[N:25][C:24]([C:22]2[S:23][C:16]3[C:17](=[N:18][CH:19]=[CH:20][C:15]=3[O:14][C:11]3[CH:12]=[CH:13][C:8]([NH:7][C:5]([NH:4][CH:1]4[CH2:3][CH2:2]4)=[O:6])=[CH:9][C:10]=3[F:36])[CH:21]=2)=[CH:29][CH:28]=1)[CH2:32][CH2:33][O:34][CH3:35])=[O:50]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44229901HCID 44229901, compound

Product 1

HCID 67048095HCID 67048095, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 339 (48 mg, 0.095 mmol), N-Boc-valine (41 mg, 0.19 mmol), and DIPEA (0.083 mL, 0.47 mmol) in DMF (20 mL) was added HATU (90 mg, 0.236 mmol). The resulting solution was stirred at r.t. for 3 h. The reaction mixture was partitioned between ethyl acetate and water, washed with 1M HCl and brine, dried (MgSO4), filtered and concentrated to yield the crude, BOC-protected product. This material was dissolved in dichloromethane (75 mL) and trifluoroacetic acid (3 mL), and stirred at r.t. for 3 h. The mixture was then concentrated and the residue was purified by Gilson reverse phase HPLC (35-95% MeOH/H2O, Aquasil C18, 30 min) and lyophilized. The residue (containing some formic acid from the HPLC) was partitioned between dichloromethane and 1M NaOH. The organic phase was dried (MgSO4), filtered and concentrated to give 341 (18 mg, 50% yield) as a 7:3 mixture of rotamers by 1H NMR. 1H NMR (DMSO-d6) δ(ppm) 1H: 8.73 (s, 1H); 8.57-8.51 (m, 2H); 8.36 (s, 0.3H); 8.32 (s, 0.7H); 8.29-8.24 (m, 1H); 7.84-7.71 (m, 2H); 7.38 (t, J=8.8, 1H); 7.21 (d, J=8.3, 1H); 6.66-6.64 (m, 1H); 6.59 (s, 1H); 4.90 (d, J=17.6, 0.3H); 4.73 (d, J=15.6, 0.7H); 4.64 (d, J=17.1, 0.3H); 4.53 (d, J=15.6, 0.7H); 3.73-3.39 (m, 5H); 3.25 (s, 2.2H); 3.22 (s, 1.1H); 2.58-2.52 (m, 1H); 1.80-1.70 (m, 1H); 0.89-0.84 (m, 6H); 0.68-0.64 (m, 2H); 0.45-0.41 (m, 2H). LRMS: (M+H) 607.5.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washwashed with 1M HCl and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto yield the crude, BOC-protected product
  7. concentrationThe mixture was then concentrated
  8. customthe residue was purified by Gilson reverse phase HPLC (35-95% MeOH/H2O, Aquasil C18, 30 min)
  9. additionThe residue (containing some formic acid from the HPLC)
  10. customwas partitioned between dichloromethane and 1M NaOH
  11. dry with materialThe organic phase was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-ca5ad20b834344dc81636d619c98a560
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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