Diisopropylethylamine → HCID 86702805, compound

HRID 1425944Notes

Reaction equation

HRID 1425944 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:24][C:25]1[CH:26]=[CH:27][C:28]2[C:32]([CH3:34])([CH3:33])[O:31][B:30]([OH:35])[C:29]=2[CH:36]=1.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>C(Cl)Cl.CCCCCC.CCOC(C)=O>[OH:35][B:30]1[C:29]2[CH:36]=[C:25]([NH:24][C:10](=[O:11])[C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:21])[F:23])=[CH:16][CH:15]=3)[CH:26]=[CH:27][C:28]=2[C:32]([CH3:34])([CH3:33])[O:31]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 273619882317-83-7HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583731006-amino-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol

Product 1

HCID 86702805HCID 86702805, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of (R)-2-(tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid (LXVI) (1.17 g, 3.5 mmol) and 6-amino-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol (XCVIII) (0.62 g, 3.5 mmol) in DCM (35 mL) were added DIPEA (1 mL, 5.3 mmol) and HATU (1.4 g, 3.7 mmol). The mixture was stirred overnight at room temperature. The reaction mixture was diluted with DCM and washed sequentially with 1 M aqueous HCl, 1 M aqueous NaOH, and brine, and was dried over MgSO4. The solvent was evaporated and the crude product was purified by flash chromatography using on a first column (DCM/MeOH 500/1→300/1→200/1→100/1), and on a second column (hexane/EtOAc 5/1→4/1→3/1), to give 1.00 g of pure (R)-tert-butyl 1-(1-hydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborol-6-ylamino)-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (CLXII) as an off-white solid (1.0 g, 2.03 mmol, 60% yield). 1H NMR (CDCl3) δ ppm 1.40 (s, 9H), 1.50 (s, 6H), 3.13 (dd, J=13 Hz, J=14 Hz, 1H), 3.27 (dd, J=13 Hz, J=13 Hz, 1H), 4.48-4.60 (brs, 1H), 5.13-5.26 (brs, 1H), 7.17 (d, J=8 Hz, 1H), 7.26 (d, J=2 Hz, 1H), 7.36 (d, J=5 Hz, 2H), 7.55 (d, J=5 Hz, 2H), 7.58 (d, J=8 Hz, 1H), 8.11-8.16 (brs, 1H); 19F NMR (CDCl3) δ ppm −61.88 (s, 3F); ESIMS found for C24H28BF3N2O5 m/z 493.6 (M+H).

Workup

  1. washwashed sequentially with 1 M aqueous HCl, 1 M aqueous NaOH, and brine
  2. dry with materialwas dried over MgSO4
  3. customThe solvent was evaporated
  4. customthe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-49a70123534643c6af2be040c73c590b
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

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