Diisopropylethylamine → HCID 178455280, compound

HRID 2169369Notes

Reaction equation

HRID 2169369 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[CH2:48][CH2:47][O:46][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.O>[Si:32]([O:39][CH2:40][CH2:41][N:42]([CH:43]1[CH2:48][CH2:47][O:46][CH2:45][CH2:44]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)[CH2:21][CH2:20][CH2:19][CH2:18]2)[N:11]=1)=[O:31])([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33]

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 86725984[2-(Tert-butyl-dimethylsilanyloxy)-ethyl]-(tetrahydro-pyran-4-yl)-amineHCID 178524871HCID 178524871, compound

Product 1

HCID 178455280HCID 178455280, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

5-Benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid (324) (150 mg, 0.34 mmol) and [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-(tetrahydro-pyran-4-yl)-amine (8j) were taken up in dimethylformamide (3 ml). HATU (195.2 mg, 0.51 mmol) and N,N-diisopropylethylamine (110.4 mg, 0.86 mmol) were added at room temperature and the reaction mixture was stirred for 16 h (monitored by LC-MS). To the reaction, water was added (10 ml) and the mixture was stirred for 5 min. Thereafter, the aqueous mixture was extracted with ethyl acetate (2×15 ml) and 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]-(tetrahydro-pyran-4-yl)-amide (333) (130 mg, 56%) as a yellow sticky solid.

Workup

  1. additionwas added (10 ml)
  2. stirringthe mixture was stirred for 5 min
  3. extractionThereafter, the 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-9042023df22546968a381057e10b5068
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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