Hydrochloric Acid → HCID 86667427, compound

HRID 74975Notes

Reaction equation

HRID 74975 reaction equation
[NH2:1][CH2:2][C@:3]1([OH:18])[CH2:8][CH2:7][CH2:6][C@H:5]([NH:9][C:10]2[C:15]([F:16])=[CH:14][N:13]=[C:12]([Cl:17])[N:11]=2)[CH2:4]1.CCN(C(C)C)C(C)C.[C:28](Cl)(=[O:30])[CH3:29].Cl.[OH-].[Na+]>ClCCl>[Cl:17][C:12]1[N:11]=[C:10]([NH:9][C@H:5]2[CH2:6][CH2:7][CH2:8][C@:3]([CH2:2][NH:1][C:28](=[O:30])[CH3:29])([OH:18])[CH2:4]2)[C:15]([F:16])=[CH:14][N:13]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 86667425(1S,3S)-1-(aminomethyl)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol2×

Product 1

HCID 86667427HCID 86667427, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(1S,3S)-1-(aminomethyl)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexanol, 46b, (0.19 g, 0.69 mmol) was dissolved in dichloromethane (15 mL) and treated with DIPEA (1.20 mL, 6.91 mmol) and acetyl chloride (0.10 mL, 1.38 mmol). After 5 minutes, the reaction mixture was diluted into 1N HCl (30 mL), and the aqueous layer was brought to a basic pH by addition of 1N NaOH. The resulting suspension was extracted with dichloromethane (50 mL). The organic layer was dried on Na2SO4 and concentrated in vacuo to provide the crude product, which was purified by silica gel chromatography (20-100% EtOAc/hexanes gradient) to afford 195 mg of N-{[(1S,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)-1-hydroxycyclo-hexyl]methyl}acetamide as a white foamy solid. LCMS RT=2.82 (M+1) 317.33.

Workup

  1. extractionThe resulting suspension was extracted with dichloromethane (50 mL)
  2. customThe organic layer was dried on Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto provide the crude product, which
  5. customwas purified by silica gel chromatography (20-100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-341a0b7f201b4c90a78a2a62ad77b9be
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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