Diisopropylethylamine → HCID 178484768, compound

HRID 2169384Notes

Reaction equation

HRID 2169384 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:32]([OH:34])=O)=[N:11][C:12]([CH2:16][C:17]2([C:22]3[C:31]4[C:26](=CC=[CH:29][CH:30]=4)[CH:25]=[CH:24][CH:23]=3)[CH2:21][CH2:20][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.[CH:35](N(CC)C(C)C)(C)[CH3:36].[Si:44]([O:51][CH2:52][CH2:53][NH:54][CH3:55])([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45].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>[Si:44]([O:51][CH2:52][CH2:53][N:54]([CH3:55])[C:32]([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:22]3[C:31]4[C:26](=[CH:25][CH:24]=[CH:29][CH:30]=4)[CH:36]=[CH:35][CH:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:34])([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:45])[CH3:46]

Participants

7

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 16203640N-(2-(tert-Butyldimethylsilyloxy)ethyl)methylamineHCID 178524864HCID 178524864, compound

Product 1

HCID 178484768HCID 178484768, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (345) (300 mg, 0.66 mmol) in dimethylformamide (7.5 mL) were added N,N-diisopropylethylamine (0.33 mL, 1.98 mmol), [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amine (8a) (187 mg, 0.99 mmol) and HATU (301 mg, 0.79 mmol) and the reaction mixture was stirred at room temperature for 1.5 h (silica TLC, 50% ethyl acetate in hexane/SiO2/UV, Rf=0.6) The reaction mass was diluted with ethyl acetate (100 ml) and washed with brine (3×50 mL). The organic phase was thereafter dried and concentrated in vacuo to get a crude mass which was purified by Combi-Flash using a mixture of ethyl acetate and hexane as eluting solvent to get pure 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amide (350) (310 mg, 75%) as a light yellow sticky solid.

Workup

  1. washwashed with brine (3×50 mL)
  2. customThe organic phase was thereafter dried
  3. concentrationconcentrated in vacuo
  4. customto get a crude mass which
  5. customwas purified by Combi-Flash
  6. additiona mixture of ethyl acetate and hexane
  7. washas eluting solvent

Sources & evidence

ORD record
ord-3a5e2a04e0d24905a3e4702fcbcbcd10
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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