Diisopropylethylamine → HCID 178486791、化合物

HRID 2064611ノート

反応式

HRID 2064611 の反応式
N1C=CC=C(CNC(C2C=CC3NC(C4C(C(=O)NC(C)C)=CNN=4)=NC=3C=2)=O)C=1.[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH2:45])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1.C(N(C(C)C)CC)(C)C.[N:58]1([C:64](Cl)=[O:65])[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]1>O1CCCC1>[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH:45][C:64]([N:58]4[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]4)=[O:65])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 178457736HCID 178457736、化合物HCID 178486793HCID 178486793、化合物

生成物 1

HCID 178486791HCID 178486791、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

By proceeding in a manner similar to Example 248(a) above but (i) treating a solution of 3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine [0.2 g, Example 233(e)] and diisopropylethylamine (392 mg, 4 eq) in tetrahydrofuran (25 mL) with piperidinecarbonyl chloride (450 mg, 4 eq), stirring overnight at ambient temperature, and evaporating the reaction mixture, (ii) triturating the reaction product with water (30 mL) and ethyl acetate (50 mL) and extracting with aqueous layer with ethyl acetate, (iii) combining the organic phases, drying over magnesium sulfate, then evaporating (iv) chromatographing the residue on silica gel (ethyl acetate), (v) triturating the partially purified material with ethyl acetate (15 mL) for 1.5 hours and filtering, and (vi) evaporating the filtrate and chromatographing the residue on silica gel (ethyl acetate/heptane gradient of 20-0%) there was prepared piperidine-1-carboxylic acid[3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-amide (50 mg) as a yellow solid, mp>310° C. LC-MS (Method E) RT=3.25 minutes, 374 (M+H)+.

後処理

  1. customevaporating the reaction mixture, (ii)
  2. customtriturating the reaction product with water (30 mL) and ethyl acetate (50 mL)
  3. extractionextracting with aqueous layer with ethyl acetate, (iii)
  4. dry with materialdrying over magnesium sulfate
  5. customevaporating (iv) chromatographing the residue on silica gel (ethyl acetate), (v)
  6. customtriturating the partially purified material with ethyl acetate (15 mL) for 1.5 hours
  7. filtrationfiltering
  8. custom(vi) evaporating the filtrate and chromatographing the residue on silica gel (ethyl acetate/heptane gradient of 20-0%) there
  9. customwas prepared piperidine-1-carboxylic acid[3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-amide (50 mg) as a yellow solid, mp>310° C

出典と根拠

ORDレコード
ord-f6b86ef24e9c48ab826992e5d1fbfc41
出典データセット
uspto-grants-2012_10
特許番号
US08288425B2

反応ノート

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