Hydrochloric Acid → 1-[5-[2-(Ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712333ノート

反応式

HRID 712333 の反応式
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([C:18]3[CH:19]=[N:20][C:21]([N:24]4[CH2:29][CH2:28][C:27]([CH3:35])([C:30]([O:32]CC)=[O:31])[CH2:26][CH2:25]4)=[N:22][CH:23]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2].[OH-].[Na+].Cl.C(Cl)Cl>C(O)C.O>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([C:18]3[CH:19]=[N:20][C:21]([N:24]4[CH2:25][CH2:26][C:27]([CH3:35])([C:30]([OH:32])=[O:31])[CH2:28][CH2:29]4)=[N:22][CH:23]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 86664042Ethyl 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

生成物 1

HCID 866640431-[5-[2-(Ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
60 °C

実験手順

Ethyl 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (101 mg, 0.20 mmol) was suspended in ethanol (2 mL) and sodium hydroxide solution (2 mL, 1 M, aq) was added to give a pale yellow solution and the mixture heated to 60° C. for 1 h 40 minutes then left to cool to rt overnight. The mixture was acidified to pH 3 with HCl solution (1 M, aq) and diluted with water. DCM was added but the material did not dissolve so the mixture was concentrated under reduced pressure to remove the DCM then filtered through a PTFE filter (the filter was treated with ˜2 mL DCM to make it more permeable to aqueous suspensions) and rinsed with water (2 mL). A white solid was obtained which was dried in a vacuum oven at 40° C. to give Compound 198, 75 mg (79%). 1H NMR (DMSO): δ 1.11 (3H, t, J=7.1 Hz), 1.21 (3H, s), 1.40 (2H, ddd, J=13.8, 9.9 and 3.8 Hz), 2.02 (2H, dt, J=13.8 and 3.8 Hz), 3.20 (2H, dt, J=12.8 and 7.1 Hz), 3.33 (2H, m), 3.83 (3H, s), 4.28 (2H, dt, J=13.8 and 4.5 Hz), 6.71 (1H, br t, J=5.7 Hz), 7.56 (1H, s), 7.65 (1H, s), 8.53 (2H, s), 10.56 (1H, br s), 12.44 (1H, br s). MS: 471.13 [M+H]+.

後処理

  1. customto give a pale yellow solution
  2. waitthen left
  3. temperatureto cool to rt overnight
  4. dissolutionthe material did not dissolve so the mixture
  5. concentrationwas concentrated under reduced pressure
  6. customto remove the DCM
  7. filtrationthen filtered through a PTFE
  8. filtrationfilter (the filter
  9. additionwas treated with ˜2 mL DCM
  10. washrinsed with water (2 mL)
  11. customA white solid was obtained which
  12. customwas dried in a vacuum oven at 40° C.

出典と根拠

ORDレコード
ord-694386ced55b4733952a8188b1c4f4a1
出典データセット
uspto-grants-2015_11
特許番号
US09181234B2

反応ノート

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