Chloroacetyl chloride → HCID 66823093, compound

HRID 473589Notes

Reaction equation

HRID 473589 reaction equation
C(O[C:6](=O)[NH:7][CH2:8][CH2:9][NH:10][CH:11]1[CH2:14][N:13]([C:15]([C:17]2[S:21][C:20]3[CH:22]=[C:23]([C:26]([F:29])([F:28])[F:27])[CH:24]=[CH:25][C:19]=3[CH:18]=2)=[O:16])[CH2:12]1)(C)(C)C.CCN(CC)CC.ClC[C:40](Cl)=[O:41].C([O-])([O-])=O.[K+].[K+].Br[C:50]1[N:55]=[CH:54][CH:53]=[CH:52][N:51]=1>C(Cl)Cl>[N:51]1[CH:52]=[CH:53][CH:54]=[N:55][C:50]=1[N:7]1[CH2:8][CH2:9][N:10]([CH:11]2[CH2:14][N:13]([C:15]([C:17]3[S:21][C:20]4[CH:22]=[C:23]([C:26]([F:27])([F:29])[F:28])[CH:24]=[CH:25][C:19]=4[CH:18]=3)=[O:16])[CH2:12]2)[C:40](=[O:41])[CH2:6]1

Participants

7

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 783452-BromopyrimidineHCID 66823319HCID 66823319, compound

Product 1

HCID 66823093HCID 66823093, compoundYield 22.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1g (30 mg, 0.068 mmol) and Et3N (0.04 mL, 0.28 mmol) in CH2Cl2 (3 mL) at 0° C. was added chloroacetyl chloride (11.5 mg, 0.10 mmol). The reaction was stirred at 0° C. for 1.5 h, and was then quenched with aq. NaHCO3. The resulting mixture was extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. The resulting residue was stirred with TFA (0.5 mL) in CH2Cl2 (2 mL) for 1.5 h. The solution was concentrated, and the residue was stirred in aq. NaHCO3 (2 mL) and THF (3 mL) for 24 h. To the resulting intermediate 1h in this mixture of aq. NaHCO3 and THF was added K2CO3 (28 mg, 0.20 mmol) and 2-bromopyrimidine (32 mg, 0.20 mmol). The reaction mixture was heated to reflux for 16 h, and was then extracted with CH2Cl2. The organic solution was dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, 3% MeOH/CH2Cl2) gave Cpd 23 as a white solid (7 mg). MS 462 (M+H+).

Workup

  1. customwas then quenched with aq. NaHCO3
  2. extractionThe resulting mixture was extracted with CH2Cl2
  3. dry with materialThe organic solution was dried over Na2SO4
  4. concentrationconcentrated
  5. stirringThe resulting residue was stirred with TFA (0.5 mL) in CH2Cl2 (2 mL) for 1.5 h
  6. concentrationThe solution was concentrated
  7. stirringthe residue was stirred in aq. NaHCO3 (2 mL)
  8. waitTHF (3 mL) for 24 h
  9. additionTo the resulting intermediate 1h in this mixture of aq. NaHCO3 and THF
  10. temperatureThe reaction mixture was heated
  11. temperatureto reflux for 16 h
  12. extractionwas then extracted with CH2Cl2
  13. dry with materialThe organic solution was dried over Na2SO4
  14. concentrationconcentrated
  15. customPurification by column chromatography (silica gel, 3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-290a3f5b16f548c18ea2bb1b042d1688
Source dataset
uspto-grants-2014_01
Patent number
US08637498B2

Reaction notes

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