Hydrochloric Acid → HCID 57662867, compound

HRID 2420795Notes

Reaction equation

HRID 2420795 reaction equation
[NH2:1][C:2]1[N:7]2[N:8]=[C:9]3[CH2:13][S:12][CH2:11][C:10]3=[C:6]2[N:5]=[C:4]([C:14]2[C:19]([CH3:20])=[CH:18][C:17]([CH3:21])=[CH:16][C:15]=2[CH3:22])[C:3]=1[C:23]#[N:24].Cl.CO>O1CCCC1>[NH2:24][CH2:23][C:3]1[C:4]([C:14]2[C:15]([CH3:22])=[CH:16][C:17]([CH3:21])=[CH:18][C:19]=2[CH3:20])=[N:5][C:6]2[N:7]([N:8]=[C:9]3[CH2:13][S:12][CH2:11][C:10]=23)[C:2]=1[NH2:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 67214165HCID 67214165, compound

Product 1

HCID 57662867HCID 57662867, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

A suspension of 81 mg (0.24 mmol) of 4-amino-2-mesityl-7H,9H-thieno[3′,4′:3,4]pyrazolo[1,5-a]pyrimidine-3-carbonitrile from Step A in 1.2 mL of anhydrous tetrahydrofuran was stirred under nitrogen in an ultrasound bath as 1.2 mL (1.2 mmol) of 1M borane-tetrahydrofuran complex in tetrahydrofuran was added gradually by syringe. The mixture was stirred overnight with intermittent sonication. Next, the mixture was quenched by cautious gradual addition of 0.36 mL (4.32 mmol) of concentrated hydrochloric acid (gas evolution) followed by addition of 1.2 mL of methanol. The resulting solution was stirred in a sealed tube with heating in an oil bath at 80° C. for 4 h. The solution was evaporated to dryness and re-concentrated twice from methanol. The residue was converted to free base form by passage through a pre-washed SCX ion exchange cartridge. After flushing the column with methanol to remove trifluoroacetic acid, elution with 1M ammonia in methanol afforded the crude product. Further purification by flash chromatography on silica gel (elution with 98:2:0.4 dichloromethane:methanol:concentrated ammonium hydroxide) yielded the title compound. LC-MS 340 (M+1).

Workup

  1. additionwas added gradually by syringe
  2. stirringThe resulting solution was stirred in a sealed tube
  3. customThe solution was evaporated to dryness
  4. concentrationre-concentrated twice from methanol
  5. customAfter flushing the column with methanol
  6. customto remove
  7. washtrifluoroacetic acid, elution with 1M ammonia in methanol
  8. customafforded the crude product
  9. customFurther purification by flash chromatography on silica gel (elution with 98:2:0.4 dichloromethane:methanol:concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-a1aaeb98f1b94efdaa7debf8395f1cb5
Source dataset
uspto-grants-2011_06
Patent number
US07956061B2

Reaction notes

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