4-Methylmorpholine → tert-butyl 2-(2-(3-(methylthio)-1-phenyl-1H-indazol-6-ylamino)-2-oxoethyl)piperidine-1-carboxylate

HRID 68680Notes

Reaction equation

HRID 68680 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1(O)C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1.[CH3:47][S:48][C:49]1[C:57]2[C:52](=[CH:53][C:54]([NH2:58])=[CH:55][CH:56]=2)[N:51]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[N:50]=1>ClCCl>[CH3:47][S:48][C:49]1[C:57]2[C:52](=[CH:53][C:54]([NH:58][C:15](=[O:17])[CH2:14][CH:9]3[CH2:10][CH2:11][CH2:12][CH2:13][N:8]3[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:55][CH:56]=2)[N:51]([C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[N:50]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 50585361-Boc-2-Piperidineacetic AcidHCID 498399773-(methylthio)-1-phenyl-1H-indazol-6-amine

Product 1

HCID 67447087tert-butyl 2-(2-(3-(methylthio)-1-phenyl-1H-indazol-6-ylamino)-2-oxoethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
15 °C

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 2-(1-(tert-butoxycarbonyl)piperidin-2-yl)acetic acid (0.47 mg), 1H-benzo[d][1,2,3]triazol-1-ol (300 mg, 1.96 mmol), EDC.HCl (370 mg, 1.94 mmol), 4-methylmorpholine (590 mg, 5.84 mmol, 2.98 equiv) in dichloromethane (3 mL). The resulting solution was stirred for 10 min at 15° C. A solution of 3-(methylthio)-1-phenyl-1H-indazol-6-amine (500 mg, 1.96 mmol, 1.00 equiv) in dichloromethane (3 mL) was added. The resulting solution was stirred for an additional 2 h at 15° C. The resulting mixture was washed with aq. sodium bicarbonate (1×8 mL) and brine (2×8 mL). The resulting mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10˜1:3) to yield tert-butyl 2-(2-(3-(methylthio)-1-phenyl-1H-indazol-6-ylamino)-2-oxoethyl)piperidine-1-carboxylate as a white solid. MS: 481 (MH+).

Workup

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for an additional 2 h at 15° C
  4. washThe resulting mixture was washed with aq. sodium bicarbonate (1×8 mL) and brine (2×8 mL)
  5. dry with materialThe resulting mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-dca8828d9cb54e198397c918527ec81d
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Reaction notes

Loading…