Water → HCID 18613786, compound

HRID 1264896Notes

Reaction equation

HRID 1264896 reaction equation
O[CH2:2][C:3]1[N:8]=[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:6]=[C:5]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]2[CH3:27])[C:4]=1[CH3:28].C(N(S(F)(F)[F:35])CC)C.O.[Cl:39]CCl>>[ClH:39].[CH3:28][C:4]1[C:5]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:18]2[CH3:27])=[N:6][C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)=[N:8][C:3]=1[CH2:2][F:35]

Participants

5

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 123472(Diethylamino)sulfur trifluorideHCID 18315695HCID 18315695, compound

Product 1

HCID 18613786HCID 18613786, compoundYield 34.5%

Conditions

Temperature
-75 °C

Procedure

The solution of 6-hydroxymethyl-5-methyl-2-(4-fluorophenyl-amino)4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine (0.19 g, 0.5 mmol) prepared in accordance with WO 98/43968 in dichloromethane (5 ml) and cooled to −75° C. and (diethylamino)sulfur trifluoride (0.15 ml, 2.26mmol) was dropwise added thereto. The reaction mixture was stirred for 2 hours at −75° C., further stirred for 2 hours at −45 ° C., and slowly heated to room temperature. The reaction mixture was stirred for 18 hours at room temperature, and then water was added thereto to terminate the reaction. The extracted organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting residue was subjected to silica gel column column chromatography (eluent:ethyl acetate/hexane=⅓), and then treated with ethyl ether solution saturated with hydrochloric acid to afford 72 mg (34.5%) of the titled compound.

Workup

  1. stirringfurther stirred for 2 hours at −45 ° C.
  2. temperatureslowly heated to room temperature
  3. stirringThe reaction mixture was stirred for 18 hours at room temperature
  4. customto terminate
  5. customthe reaction
  6. dry with materialThe extracted organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. additiontreated with ethyl ether solution saturated with hydrochloric acid

Sources & evidence

ORD record
ord-78755dfc13134355be2b59519752f658
Source dataset
uspto-grants-2003_04
Patent number
US06545008B1

Reaction notes

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