Diisopropylethylamine → HCID 178457473, compound

HRID 2169305Notes

Reaction equation

HRID 2169305 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:33]([OH:35])=O)=[N:11][C:12]([CH2:16][C:17]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:26][CH2:25][C:20]3([O:24][CH2:23][CH2:22][O:21]3)[CH2:19][CH2:18]2)=[N:13][C:14]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Si:36]([O:43][CH2:44][CH2:45][NH:46][CH:47]([CH3:49])[CH3:48])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37].C(N(CC)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)C=O.C(OCC)(=O)C.CCCCCC>[Si:36]([O:43][CH2:44][CH2:45][N:46]([CH:47]([CH3:49])[CH3:48])[C:33]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:18][CH2:19][C:20]3([O:21][CH2:22][CH2:23][O:24]3)[CH2:25][CH2:26]2)[N:11]=1)=[O:35])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57917054N-(2-((tert-butyldimethylsilyl)oxy)ethyl)propan-2-amineHCID 178524865HCID 178524865, compound

Product 1

HCID 178457473HCID 178457473, compoundYield 72.85%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-ylmethyl)-pyrimidine-4-carboxylic acid (270) (600 mg, 1.26 mmol) in dimethylformamide (12 mL) were added [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (411 mg, 1.89 mmol), N,N-diisopropylethylamine (0.63 mL, 3.78 mmol) and HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate) (574 mg, 1.51 mmol) and stirred at room temperature for 17 h (TLC, ethyl acetate:hexane=1:1/UV/SiO2, Rf=0.6). The reaction mixture was diluted with ethyl acetate (100 mL), washed with brine (3×50 mL), dried and concentrated in vacuum to get a crude mass which was purified by normal silica gel (100-200 mesh) column chromatography using gradient polarity eluent (1-2% methanol in dichloromethane) to get pure 5-benzyloxy-6-hydroxy-2-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-ylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (271) (620 mg, 72.85%) as a brown sticky solid.

Workup

  1. washwashed with brine (3×50 mL)
  2. customdried
  3. concentrationconcentrated in vacuum
  4. customto get a crude mass which
  5. customwas purified by normal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-5db25d4b9a5d46479a35edf7e0db36b3
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

Loading…