Diisopropylethylamine → HCID 178455278, compound

HRID 2169361Notes

Reaction equation

HRID 2169361 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:29]([OH:31])=O)=[N:11][C:12]([CH2:16][C:17]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[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.[Si:32]([O:39][CH2:40][CH2:41][NH:42][CH:43]1[CH2:45][CH2:44]1)([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C)C=O.CCCCCC.O.C(OCC)(=O)C>[Si:32]([O:39][CH2:40][CH2:41][N:42]([CH:43]1[CH2:44][CH2:45]1)[C:29]([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][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:18][CH2:19][CH2:20][CH2:21]2)[N:11]=1)=[O:31])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

Participants

9

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 178524871HCID 178524871, compound

Product 1

HCID 178455278HCID 178455278, compoundYield 55.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid (324) (150.0 mg, 0.34 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amine (8d) (110.4 mg, 0.51 mmol) were taken up in dimethylformamide (3 ml), HATU (123.3 mg, 0.41 mmol) and N,N-diisopropylethylamine (132.5 mg, 1.03 mmol) were added at room temperature and stirred for 16 h while silica thin layer chromatography was performed (40% ethyl acetate in hexane; Rf=0.4). To the reaction, water (10 ml) was added and stirred for 5 min and the aqueous mixture was extracted with ethyl acetate (2×15 ml). The combined extracts were washed with water (3×10 ml), dried and concentrated under reduced pressure. The obtained crude product was purified by normal silica gel column chromatography (100-200 mesh) using 30% ethyl acetate in hexane as mobile phase to get pure 5-benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-cyclopropyl-amide (325) (120 mg, 55%) as a yellow sticky solid.

Workup

  1. additionwas added
  2. stirringstirred for 5 min
  3. extractionthe aqueous mixture was extracted with ethyl acetate (2×15 ml)
  4. washThe combined extracts were washed with water (3×10 ml)
  5. customdried
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained crude product
  8. customwas purified by normal silica gel column chromatography (100-200 mesh)

Sources & evidence

ORD record
ord-b19cebfa2a584d96a024a830722cbdef
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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