Hydrochloric Acid → 2-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-diisopropoxypyrido[2,3-d]pyrimidin-4(3H)-one

HRID 591785Notes

Reaction equation

HRID 591785 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH:12]([CH3:14])[CH3:13])[CH:8]=[C:7]([O:15][CH:16]([CH3:18])[CH3:17])[C:3]=1[C:4]([NH2:6])=[O:5].[CH3:19][C:20]1[CH:21]=[C:22]([CH:25]=[C:26]([CH3:36])[C:27]=1[O:28][CH2:29][CH2:30][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[CH:23]=O.OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1.Cl>CN(C)C(=O)C.CCOCC>[CH3:36][C:26]1[CH:25]=[C:22]([C:23]2[NH:6][C:4](=[O:5])[C:3]3[C:7]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:8][C:9]([O:11][CH:12]([CH3:13])[CH3:14])=[N:10][C:2]=3[N:1]=2)[CH:21]=[C:20]([CH3:19])[C:27]=1[O:28][CH2:29][CH2:30][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6101p-Toluenesulfonic acidHCID 23665763Sodium BisulfiteHCID 289325703,5-Dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehydeHCID 666709532-Amino-4,6-diisopropoxy-nicotinamide

Product 1

HCID 1363480262-(3,5-Dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-diisopropoxypyrido[2,3-d]pyrimidin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 2-amino-4,6-diisopropoxy-nicotinamide (450 mg, 1.78 mmol) and 3,5-dimethyl-4-(2-pyrrolidin-1-yl-ethoxy)-benzaldehyde (440 mg, 1.78 mmol) in N,N-dimethyl acetamide (10 mL) were added NaHSO3 (790 mg, 4.44 mmol) and p-TSA (845 mg, 4.44 mmol). The reaction mixture was heated at 120° C. for 16 hours, then cooled to room temperature. The solvent was removed under reduced pressure. Then, water (100 mL) was added and stirred for 30 min at room temperature. The separated solids were filtered and dried to give crude product, which was purified by the Simpliflash system, using 2% methanol in dichloromethane, to give a yellow oil, which dissolved in ether. 2N HCl in ether was added, and the separated solids were filtered and dried to give the hydrochloride salt of the title compound as a yellow solid. Yield: 59 mg (6%). 1H NMR (400 MHz, DMSO-d6): δ 10.7 (br s, 1H), 7.88 (s, 2H), 6.31 (s, 1H), 5.41 (m, 1H), 4.80 (m, 1H), 4.14 (t, J=4.8 Hz, 2H), 3.61 (m, 2H), 3.16 (m, 4H), 2.34 (s, 6H), 2.03 (m, 2H), 1.91 (m, 2H), 1.32 (s, 6H), 1.30 (s, 6H). MS (ES) m/z: 481.18 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed under reduced pressure
  3. additionThen, water (100 mL) was added
  4. filtrationThe separated solids were filtered
  5. customdried
  6. customto give crude product, which
  7. customwas purified by the Simpliflash system
  8. customto give a yellow oil, which
  9. filtrationthe separated solids were filtered
  10. customdried

Sources & evidence

ORD record
ord-4f9f3e7121ff41bdaffdc70613e5a04a
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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