Formic Acid → (1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-2-oxo-1-(pyridin-2-ylmethyl)ethylformamide

HRID 1830607Notes

Reaction equation

HRID 1830607 reaction equation
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[NH:11]1[C:19]2[C:14](=[C:15]([N:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:36])[C@H:27]([NH2:35])[CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH2:22][CH2:21]3)[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1.N1(C2C=CC=C3C=2C=CN3)CCNCC1.C(OC(N[C@H](CC1C=CC=CN=1)C(O)=O)=O)(C)(C)C>C1COCC1.C(OCC)(=O)C>[NH:11]1[C:19]2[C:14](=[C:15]([N:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:36])[C@H:27]([NH:35][CH:1]=[O:2])[CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[CH2:22][CH2:21]3)[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1

Participants

8

Reactant 5

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 5945904-(piperazin-1-yl)-1H-indoleHCID 7019139(2R)-2-{[(tert-butoxy)carbonyl]amino}-3-(pyridin-2-yl)propanoic acidHCID 58651199(1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-2-oxo-1-(pyridin-2-ylmethyl)ethylamine

Product 1

HCID 58651198(1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-2-oxo-1-(pyridin-2-ylmethyl)ethylformamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of formic acid (0.9 mL; 24 mmol) and acetic anhydride (1.8 mL; 19.5 mmol) was stirred at 60° C. for 4 hours, then cooled to ambient temperature. The resulting mixed anhydride was added to a −10° C. solution of (1R)-2-[4-(1H-indol-4-yl)piperazin-1-yl]-2-oxo-1-(pyridin-2-ylmethyl)ethylamine (prepared in two steps from 4-piperazin-1-yl-1H-indole and (2R)-2-[(tert-butoxycarbonyl)amino]-3-pyridin-2-ylpropanoic acid according to the procedures outlined in examples 1 and 2) (1.07 g.; 3.0 mmol) in THF (30 mL). The mixture was allowed to warm to ambient temperature over 3 hours, diluted with ethyl acetate, and washed with saturated aqueous Na2CO3. The organic layer was dried over MgSO4, filtered, and the solvent removed in vacuo. The crude residue was purified by flash chromatography to afford the title compound as a beige solid foam (720 mg.; 64%). MS EI M+.@ m/z 377; 1H NMR, 400 MHz, DMSO-d6.

Workup

  1. temperaturecooled to ambient temperature
  2. temperatureto warm to ambient temperature over 3 hours
  3. washwashed with saturated aqueous Na2CO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe crude residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a590c645a5b64d0c8195ee1b74806605
Source dataset
uspto-grants-2006_06
Patent number
US07067518B2

Reaction notes

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