Diisopropylethylamine → HCID 178455281, compound

HRID 2169480Notes

Reaction equation

HRID 2169480 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28](O)=[O:29])=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N: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.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.[Si:64]([O:71][CH2:72][CH2:73][NH:74][CH:75]1[CH2:77][CH2:76]1)([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]([CH:75]1[CH2:76][CH2:77]1)[C:28]([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[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:29])([C:67]([CH3:70])([CH3:69])[CH3:68])([CH3:66])[CH3:65]

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 86699774N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropanamineHCID 178524873HCID 178524873, compound

Product 1

HCID 178455281HCID 178455281, compoundYield 54%

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) (150 mg, 0.494 mmol) in dimethylformamide (5 mL), N,N-diisopropylethylamine (0.184 mL, 1.111 mmol), HATU (211.24 mg, 0.556 mmol) and [2-(tert-Butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amine (crude) (8d) (239 mg) were added. This reaction mixture was allowed to stir for 16 h at room temperature while silica thin layer chromatography was performed (50% ethyl acetate in hexane; Rf=0.5) The reaction was quenched with ice cold water (25 mL) and extracted with ethyl acetate (2×30 mL). The organic part was dried, then concentrated and the crude product was purified by normal 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-carboxylicacid[2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amide (450) (120 mg, 54%) as a yellow sticky liquid.

Workup

  1. customwas quenched with ice cold water (25 mL)
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. customThe organic part was dried
  4. concentrationconcentrated
  5. customthe crude product was purified by normal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-d076da51050d4d54b083f5bdc4e5f8fb
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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