Diisopropylethylamine → HCID 178441572, compound

HRID 1051000Notes

Reaction equation

HRID 1051000 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.[C:11]([C:15]1[N:20]=[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][C@H:29]3[CH2:34][CH2:33][C@H:32]([NH2:35])[CH2:31][CH2:30]3)[CH2:23][CH2:22]2)[CH:18]=[C:17]([CH:36]2[CH2:39][CH2:38][CH2:37]2)[N:16]=1)([CH3:14])([CH3:13])[CH3:12].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl>[C:11]([C:15]1[N:20]=[C:19]([N:21]2[CH2:22][CH2:23][N:24]([CH2:27][CH2:28][C@H:29]3[CH2:30][CH2:31][C@H:32]([NH:35][C:8]([C@H:5]4[CH2:4][CH2:3][C@H:2]([OH:1])[CH2:7][CH2:6]4)=[O:10])[CH2:33][CH2:34]3)[CH2:25][CH2:26]2)[CH:18]=[C:17]([CH:36]2[CH2:39][CH2:38][CH2:37]2)[N:16]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

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 178441571HCID 178441571, compoundHCID 178525780HCID 178525780, compound

Product 1

HCID 178441572HCID 178441572, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trans-4-hydroxycyclohexanecarboxylic acid (1,991 g, 13.81 mmol) was added to a solution of trans-4-(2-(4-(2-(tert-butyl)-6-cyclobutylpyrimidin-4-yl)piperazin-1-yl)ethyl)cyclohexanamine (4.6 g, 11.51 mmol) in dichloromethane. HATU (2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate, 5.25 g, 13.8 mmol) and diisopropylethylamine (6.03 mL, 34.5 mmol) were added and the mixture stirred at room temperature for 14 h. The solvent was evaporated and the residue partitioned between dichloromethane and water. The aqueous phase was extracted several times with dichloromethane. The combined organic layers were washed twice with 5% aqueous sodium bicarbonate solution and twice with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. Purification via silica gel chromatography (330 g Reveleris NP cartridge) with di-chloromethane/methanol (0-80%) as eluent yielded 6.05 g of the title compound.

Workup

  1. customThe solvent was evaporated
  2. customthe residue partitioned between dichloromethane and water
  3. extractionThe aqueous phase was extracted several times with dichloromethane
  4. washThe combined organic layers were washed twice with 5% aqueous sodium bicarbonate solution and twice with saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customPurification via silica gel chromatography (330 g Reveleris NP cartridge) with di-chloromethane/methanol (0-80%) as eluent

Sources & evidence

ORD record
ord-11e4a2e928a048f59c01cd15ee02e290
Source dataset
uspto-grants-2016_07
Patent number
US09388148B2

Reaction notes

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