Acetyl chloride → HCID 178492200, compound

HRID 511028Notes

Reaction equation

HRID 511028 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:25][CH3:26])=[C:7]([CH:13]([NH:15][C:16]3[N:24]=[CH:23][N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)[CH3:14])[CH:8]=[C:9]([Cl:12])[C:10]=2[Cl:11])[CH2:2]1.CCN(C(C)C)C(C)C.[C:36](Cl)(=[O:38])[CH3:37].[OH-].[Na+]>C(#N)C.CO>[C:36]([N:1]1[CH2:2][CH:3]([C:5]2[C:6]([O:25][CH3:26])=[C:7]([CH:13]([NH:15][C:16]3[N:24]=[CH:23][N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)[CH3:14])[CH:8]=[C:9]([Cl:12])[C:10]=2[Cl:11])[CH2:4]1)(=[O:38])[CH3:37]

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 178492198HCID 178492198, compound

Product 1

HCID 178492200HCID 178492200, compoundYield 23%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of N-[1-(3-azetidin-3-yl-4,5-dichloro-2-methoxyphenyl)ethyl]-9H-purin-6-amine (25 mg, 0.064 mmol, from Example 194, Step 8) in acetonitrile (0.3 mL) was treated with DIPEA (28 μL, 0.16 mmol) followed by acetyl chloride (5.4 μL, 0.076 mmol) and stirred at room temperature for 1 hour. The reaction mixture was treated with 1N sodium hydroxide (200 μL) and heated briefly with a heat gun. The reaction mixture was diluted with methanol and purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (6.3 mg, 23%). 1N NMR (300 MHz, DMSO-d6) δ 8.15-8.06 (m, 2H), 7.72 (s, 1H), 5.82-5.61 (m, 1H), 4.56-4.45 (m, 1H), 4.43-4.30 (m, 1H), 4.29-4.17 (m, 1H), 4.14-4.03 (m, 0.5H), 3.86 (s, 3H), 1.84-1.71 (m, 5H), 1.45 (d, J=6.8 Hz, 3H). LCMS for C19H21Cl2N6O2 (M+H)+: m/z=435.1. Found: 435.0.

Workup

  1. temperatureheated briefly with a heat gun
  2. custompurified by preparative LCMS (XBridge C18 column
  3. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-030d7738f984480c87854ab2f2ef8d87
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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