Diisopropylethylamine → HCID 178484771, compound

HRID 2169472Notes

Reaction equation

HRID 2169472 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([OH:30])=O)=[N:11][C:12]([CH2:16][C:17]2(C3C=CC=CN=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.C(N(CC)C(C)C)(C)C.CN(C(ON1N=N[C:50]2[CH:51]=[CH:52][CH:53]=[N:54][C:49]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Si:64]([O:71][CH2:72][CH2:73][NH:74][CH3:75])([C:67]([CH3:70])([CH3:69])[CH3:68])([CH3:66])[CH3:65]>CN(C)C=O.CCCCCC.C(OCC)(=O)C>[Si:64]([O:71][CH2:72][CH2:73][N:74]([CH3:75])[C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:14]([OH:15])[N:13]=[C:12]([CH2:16][C:17]2([C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][N:54]=3)[CH2:18][CH2:19][CH2:20][CH2:21]2)[N:11]=1)=[O:30])([C:67]([CH3:70])([CH3:69])[CH3:68])([CH3:65])[CH3:66]

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 16203640N-(2-(tert-Butyldimethylsilyloxy)ethyl)methylamineHCID 178524873HCID 178524873, compound

Product 1

HCID 178484771HCID 178484771, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (437) (200 mg, 0.494 mmol) in dimethylformamide (7 mL), N,N-diisopropylethylamine (0.245 mL, 1.481 mmol), HATU (281.7 mg, 0.741 mmol). and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amine (8a) were added. This reaction mixture was allowed to stir for 16 h at room temperature while silica thin layer chromatography was performed (70% ethyl acetate in hexane, Rf=0.5). The reaction mixture was quenched with ice cold water (20 mL) and extracted with ethyl acetate (2×50 mL). The organic part was dried and concentrated. The resulting crude product was purified by nor mal silica gel (100-200 mesh) column chromatography using 30-40% ethyl acetate in hexane as gradient polarity mobile phase to get 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amide (442) (220 mg, 77%) as a yellow gummy liquid.

Workup

  1. customThe reaction mixture was quenched with ice cold water (20 mL)
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. customThe organic part was dried
  4. concentrationconcentrated
  5. customThe resulting crude product was purified by nor mal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-07a7c0dd76524caf8f2d9a9f5055e120
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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