Chloroacetyl chloride → HCID 86710189, compound

HRID 2284427Notes

Reaction equation

HRID 2284427 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[N:16][C:15]3[C:14]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[N:13][C:12]([C:24]4[CH:25]=[N:26][C:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[N:28][CH:29]=4)=[N:11][C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl:38][CH2:39][C:40](Cl)=[O:41].C(N(CC)CC)C>C(Cl)Cl>[Cl:38][CH2:39][C:40]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[N:16][C:15]3[C:14]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[N:13][C:12]([C:24]4[CH:25]=[N:26][C:27]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[N:28][CH:29]=4)=[N:11][C:10]=3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1)=[O:41]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 86710176HCID 86710176, compound

Product 1

HCID 86710189HCID 86710189, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
10 °C

Procedure

To a 25 mL round bottom flask, tert-butyl (5-(7-(3-aminophenyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)pyrimidin-2-yl)carbamate (Example 7, Step 2) (0.15 g, 0.0003 mol), chloroacetyl chloride (0.051 g, 0.00045 mol) and DCM (10 mL) were added and then cooled to 10° C. To the same reaction flask, triethylamine (0.12 mL, 0.0009 mol) was added. The reaction mass was stirred at room temperature for 30 minutes. The reaction mixture was diluted with DCM, washed with water and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated to provide the crude product. The crude product was purified by column chromatography (60-120 silica-gel and 0-2% methanol in chloroform) to afford the title compound (0.15 g, 87%). 1H NMR (300 MHz, DMSO-d6): δ 10.52 (s, 1H), 10.42 (s, 1H), 9.48 (s, 1H), 9.08 (d, J=1.8 Hz, 1H), 8.33 (d, J=2.1 Hz, 1H), 8.18 (s, 1H), 7.68 (t, J=4.8 Hz, 2H), 7.57 (t, J=7.8 Hz, 1H), 4.65-4.52 (br s, 4H), 4.33 (s, 2H), 3.84 (s, 4H), 1.49 (s, 9H): LC-MS (ESI): Calculated mass. 576.2, Observed mass [M+H]+: 577.2 (RT=1.53 min).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customevaporated
  4. customto provide the crude product
  5. customThe crude product was purified by column chromatography (60-120 silica-gel and 0-2% methanol in chloroform)

Sources & evidence

ORD record
ord-4ba4429d73804a5a9c0a053adaadfe04
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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