Diisopropylethylamine → HCID 178486791, 화합물

HRID 2064611노트

반응식

HRID 2064611 반응식
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

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 178457736HCID 178457736, 화합물HCID 178486793HCID 178486793, 화합물

생성물 1

HCID 178486791HCID 178486791, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-f6b86ef24e9c48ab826992e5d1fbfc41
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288425B2

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