Diisopropylethylamine → HCID 178486791, compound

HRID 2064611Notes

Reaction equation

HRID 2064611 reaction equation
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

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 178457736HCID 178457736, compoundHCID 178486793HCID 178486793, compound

Product 1

HCID 178486791HCID 178486791, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-f6b86ef24e9c48ab826992e5d1fbfc41
Source dataset
uspto-grants-2012_10
Patent number
US08288425B2

Reaction notes

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