Hydrochloric Acid → HCID 86651549, compound

HRID 1484908Notes

Reaction equation

HRID 1484908 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([C:16]#[CH:17])=[CH:14][N:13]=[C:12]([C:18]4[S:22][C:21]([C:23]#N)=[CH:20][CH:19]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[C:25]([O-])([O-])=[O:26].[K+].[K+].[ClH:31].C[OH:33]>>[ClH:31].[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([C:16]#[CH:17])=[CH:14][N:13]=[C:12]([C:18]4[S:22][C:21]([C:23]([O:26][CH3:25])=[O:33])=[CH:20][CH:19]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 11430Potassium CarbonateHCID 50943611HCID 50943611, compound

Product 1

HCID 86651549HCID 86651549, compoundYield 22%

Conditions

Temperature
20 °C

Procedure

To a solution of 5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-ethynylpyrimidin-2-yl)thiophene-2-carbonitrile (80 mg, 0.24 mmol, 1.0 equiv.) in MeOH (5 mL) was added K2CO3 (133 mg, 0.96 mmol, 4.0 eq). After being stirred at 20° C. for 4 h, HCl (10%, 5 mL) was added, and the reaction mixture was stirred at 20° C. for 30 min. The reaction mixture was extracted with ethyl acetate, the organic layer was washed with water, dried (Na2SO4) and evaporated and crystallized with petroleum ether/ethyl acetate to afford the product compound methyl 5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-ethynylpyrimidin-2-yl)thiophene-2-carboxylate hydrochloride (Compound 151 (21.2 mg, 22%). LC-MS (m/z)=366 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.75-0.79 (m, 2H), 0.99-1.02 (m, 2H), 1.95-1.99 (m, 1H), 3.87 (s, 3H), 4.92 (s, 1H), 6.46 (s, 1H), 7.85 (dd, J=4.0 Hz, J=3.6 Hz, 2H), 8.54 (s, 1H), 8.99 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred at 20° C. for 30 min
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with water
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customcrystallized with petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-522b711f7bc54b8f89aa43cd1e00ed49
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

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