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

HRID 591785ノート

反応式

HRID 591785 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒2 回HCID 31374Dimethylacetamide溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-4f9f3e7121ff41bdaffdc70613e5a04a
出典データセット
uspto-grants-2016_01
特許番号
US09238640B2

反応ノート

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