Triethylamine → 4-{4-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylcarbamoyl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 1640999Notes

Reaction equation

HRID 1640999 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]([OH:21])=O)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[F:28][C:29]1[CH:30]=[C:31]([S:36]([C:39]2[CH:40]=[C:41]3[C:45](=[CH:46][CH:47]=2)[N:44]([C:48]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[N:43]=[C:42]3[NH2:67])(=[O:38])=[O:37])[CH:32]=[C:33]([F:35])[CH:34]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]2[CH:18]=[C:17]([C:19](=[O:21])[NH:67][C:42]3[C:41]4[C:45](=[CH:46][CH:47]=[C:39]([S:36]([C:31]5[CH:30]=[C:29]([F:28])[CH:34]=[C:33]([F:35])[CH:32]=5)(=[O:38])=[O:37])[CH:40]=4)[N:44]([C:48]([C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=4)([C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)[C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[N:43]=3)[CH:16]=[N:15]2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 534858971-(1-((tert-butoxy)carbonyl)piperidin-4-yl)-1H-pyrazole-4-carboxylic acidHCID 667370025-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylamine

Product 1

HCID 667365354-{4-[5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylcarbamoyl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-(4-carboxy-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (200 mg, 0.677 mmol) in dry dichloromethane (6 mL), at 0° C., under argon, were added two drops of N,N-dimethylformamide and 62 microL of oxalyl chloride (1.05 eq). After 15 minutes the volatiles were removed under reduced pressure at room temperature. The crude acyl chloride thus obtained was dissolved under argon into dry tetrahydrofuran (5 mL), cooled to 0° C. and treated with a solution of 5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylamine (300 mg, 0.85 eq) and triethylamine (0.28 mL, 3 eq) in dry tetrahydrofuran (7 mL). The mixture was allowed to warm to room temperature overnight then evaporated to dryness. The residue was dissolved into dichloromethane, washed with water and with a saturated solution of sodium hydrogenocarbonate, dried over sodium sulphate and evaporated to dryness to give the crude title compound that was used as such for the next step without further purification.

Workup

  1. customAfter 15 minutes the volatiles were removed under reduced pressure at room temperature
  2. customThe crude acyl chloride thus obtained
  3. temperatureto warm to room temperature overnight
  4. customthen evaporated to dryness
  5. dissolutionThe residue was dissolved into dichloromethane
  6. washwashed with water and with a saturated solution of sodium hydrogenocarbonate
  7. dry with materialdried over sodium sulphate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-43256044fa8441569898fc47c85a11ad
Source dataset
uspto-grants-2012_02
Patent number
US08114865B2

Reaction notes

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