Ethyl chloroformate → 6-Chloro-5-(difluoromethyl)-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064222ノート

反応式

HRID 2064222 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[C:5]([NH2:21])=[CH:4][C:3]=1[CH:22]([F:24])[F:23].C(N(CC)C(C)C)(C)C.Cl[C:35](OCC)=[O:36]>O1CCCC1>[ClH:1].[Cl:1][C:2]1[C:3]([CH:22]([F:24])[F:23])=[CH:4][C:5]2[NH:21][C:35](=[O:36])[N:8]([CH:9]3[CH2:10][CH2:11][N:12]([CH:15]4[CH2:16][CH2:17][O:18][CH2:19][CH2:20]4)[CH2:13][CH2:14]3)[C:6]=2[CH:7]=1

参加物

5

反応物 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 598501795-Chloro-4-(difluoromethyl)-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,2-benzenediamine

生成物 1

HCID 692365546-Chloro-5-(difluoromethyl)-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride収率 87.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
150 °C

実験手順

A stirred solution of 5-chloro-4-(difluoromethyl)-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,2-benzenediamine (D98, 180 mg, 0.50 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with N,N-diisopropylethylamine (0.18 ml, 1.0 mmol) followed by ethyl chloroformate (65 mg, 0.60 mmol) and maintained for 1 hr. The solution was concentrated under vacuum and the residue dissolved in dimethylformamide (5 ml) and heated at 150° C. under argon for 1.5 hrs. The solution was concentrated under vacuum and the residue treated with 10% Na2CO3 solution and extracted with ethyl acetate. The extract was dried and concentrated under vacuum to leave an orange solid, which was washed with diethyl ether. The remaining solid was converted to its HCl salt, which was again washed with diethyl ether to afford the HCl salt of the title compound as a pale yellow solid (92 mg, 47%).

後処理

  1. temperaturemaintained for 1 hr
  2. concentrationThe solution was concentrated under vacuum
  3. dissolutionthe residue dissolved in dimethylformamide (5 ml)
  4. concentrationThe solution was concentrated under vacuum
  5. additionthe residue treated with 10% Na2CO3 solution
  6. extractionextracted with ethyl acetate
  7. customThe extract was dried
  8. concentrationconcentrated under vacuum
  9. customto leave an orange solid, which
  10. washwas washed with diethyl ether
  11. washwas again washed with diethyl ether

出典と根拠

ORDレコード
ord-69b087f87c0f44fdaaa9b95267c488f3
出典データセット
uspto-grants-2012_10
特許番号
US08288412B2

反応ノート

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