Acetyl chloride → HCID 89600021, compound

HRID 2277708Notes

Reaction equation

HRID 2277708 reaction equation
[NH2:1][CH:2]1[C:10]2[CH:9]=[N:8][CH:7]=[C:6]([N:11]3[CH2:19][C:18]4[C:13](=[CH:14][CH:15]=[C:16]([Cl:20])[CH:17]=4)[C:12]3=[O:21])[C:5]=2[CH2:4][CH2:3]1.CCN(CC)CC.[C:29](Cl)(=[O:31])[CH3:30]>C(Cl)Cl>[Cl:20][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[C:12](=[O:21])[N:11]([C:6]1[C:5]3[CH2:4][CH2:3][CH:2]([NH:1][C:29](=[O:31])[CH3:30])[C:10]=3[CH:9]=[N:8][CH:7]=1)[CH2:19]2

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 89600512HCID 89600512, compound

Product 1

HCID 89600021HCID 89600021, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(7-amino-6,7-dihydro-5H-[2]pyrindin-4-yl)-5-chloro-2,3-dihydro-isoindol-1-one (126 mg, 0.42 mmol) and Et3N (1.0 mL) in DCM (10 mL) was added acetyl chloride (0.032 mL, 0.44 mmol) at 0° C. and stirred at 0° C. for 1 hour. The resulting mixture was extracted with EtOAc (2×100 mL) and the combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 50% EtOAc-heptane gradient to give a racemic mixture of title compound (121 mg, 85%) as light yellow solid. MS: 342.1 (M+H+). This racemic mixture was then separated by chiral HPLC to afford (−)-N-[(S or R)-4-(5-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-6,7-dihydro-5H-[2]pyrindin-7-yl]-acetamide (33 mg, example 318), MS: 342.1 (M+H+) and (+)-N—[(R or S)-4-(5-chloro-1-oxo-1,3-dihydro-isoindol-2-yl)-6,7-dihydro-5H-[2]pyrindin-7-yl]-acetamide (27 mg, example 319). MS: 342.1 (M+H)+.

Workup

  1. extractionThe resulting mixture was extracted with EtOAc (2×100 mL)
  2. washthe combined organic layers were washed with brine
  3. customdried over anhy
  4. filtrationNa2SO4, filtered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel flash chromatography
  7. washeluting with a 0 to 50% EtOAc-heptane gradient
  8. customto give

Sources & evidence

ORD record
ord-a2b1bf8f7e9b4d66822a76e80b71d76f
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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