Dimethylamine → 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-N,N,2,2-tetramethylbut-3-ynamide

HRID 333897Notes

Reaction equation

HRID 333897 reaction equation
[OH:1][C:2]([CH3:34])([CH3:33])[CH2:3][C@@:4]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([CH3:26])([CH3:25])[C:22](O)=[O:23])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.C[CH2:36][N:37](C(C)C)[CH:38](C)C.N(C)C.C1COCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[OH:1][C:2]([CH3:34])([CH3:33])[CH2:3][C@@:4]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][C:21]([CH3:26])([CH3:25])[C:22]([N:37]([CH3:38])[CH3:36])=[O:23])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

7

Reactant 5

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 498703204-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acid

Product 1

HCID 498703214-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-N,N,2,2-tetramethylbut-3-ynamideYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acid (5.0 mg, 0.011 mmol) and i-Pr2NEt (0.01 mL) in CH2Cl2 (1 mL) were added 2 M Me2NH in THF (0.1 mL, 0.2 mmol) and solid HATU (8.5 mg, 0.022 mmol). The mixture was stirred overnight at rt, concentrated and the residue purified by prep HPLC to afford 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-N,N,2,2-tetramethylbut-3-ynamide (1.0 mg, 19%). LC-MS Method 1 tR=1.65 min, m/z=491, 433; 1H NMR (CDCl3) 1.13 (s, 3H), 1.18 (s, 3H), 1.52 (d, 3H), 1.55 (s, 6H), 2.10-2.40 (5H), 2.82 (m, 1H), 5.64 (q, 1H), 6.88 (d, 2H), 7.13 (d, 2H), 7.30-7.40 (5H)

Workup

  1. concentrationconcentrated
  2. customthe residue purified by prep HPLC

Sources & evidence

ORD record
ord-5ef0046bdc174ca7804078ec974b2672
Source dataset
uspto-grants-2014_11
Patent number
US08883778B2

Reaction notes

Loading…