Diisopropylethylamine → HCID 59830728, compound

HRID 1187364Notes

Reaction equation

HRID 1187364 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:12][CH:13]1[CH:20]2[CH2:21][C:16]3([OH:23])[CH2:17][CH:18]([CH2:22][CH:14]1[CH2:15]3)[CH2:19]2.C(N(C(C)C)C(C)C)C>C(Cl)Cl.C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:12][CH:13]1[CH:14]2[CH2:22][CH:18]3[CH2:17][C:16]([OH:23])([CH2:21][CH:20]1[CH2:19]3)[CH2:15]2)=[O:5]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 28574474-Aminoadamantan-1-olHCID 122639842,6-Dichlorpyridine-3-carbonyl chloride

Product 1

HCID 59830728HCID 59830728, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2,6-dichloronicotinoyl chloride (25.2 g, 119.60 mmol) in DCM (100 mL) was added dropwise to a stirred suspension of 4-aminoadamantan-1-ol (20.00 g, 119.6 mmol) and N-Ethyldiisopropylamine (24.83 mL, 143.52 mmol) in THF (400 mL) at 20° C., over a period of 30 minutes under nitrogen. The resulting suspension was stirred at room temperature for 18 hours. The reaction mixture was diluted with EtOAc (500 mL), and washed sequentially with water (100 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2,6-dichloro-N-(5-hydroxyadamantan-2-yl)nicotinamide (20.65 g, 51%) as a white solid.

Workup

  1. washwashed sequentially with water (100 mL) and saturated brine (50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford the crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b93b7e75d89641ea842945d496179ecf
Source dataset
uspto-grants-2014_03
Patent number
US08673938B2

Reaction notes

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