Triethylamine → 4-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

HRID 1432939Notes

Reaction equation

HRID 1432939 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C:5]1=[O:17])[CH:2]=[CH2:3].[C:18]([O:22][C:23](=[O:32])[NH:24][C:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1I)([CH3:21])([CH3:20])[CH3:19].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:13]([O:12][C:10]([N:7]1[CH2:8][CH2:9][N:4]([CH:1]=[CH:2][CH2:3][C:30]2[CH:29]=[N:28][CH:27]=[CH:26][C:25]=2[NH:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:32])[C:5](=[O:17])[CH2:6]1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 544523841-(2-Propenyl)-4-tert-butyloxycarbonyl-2-piperazinone

Product 1

HCID 538781434-[3-(4-Tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

1-Allyl-4-(tert-butyloxycarbonyl)-piperazin-2-one (0.49 g, 2.0 mmol) is treated with (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester (0.64 g, 2.0 mmol), Pd(OAc)2 (14 mg, 0.06 mmol), P(o-tol)3 (37 mg, 0.12 mmol), and Et3N (0.56 mmol) in a seal tube. The mixture is stirred at 100° C. overnight, then diluted with CH2Cl2 and washed H2O (2×). The CH2Cl2 layer is concentrated and the residue is chromatographed (5% MeOH/CH2Cl2) to give a mixture of two isomers (0.40 g, 0.92 mmol). The mixture is separated into its constituent isomers upon further chromatography (EtOAc) to give 4-[3-(4-tert-butoxycarbonylamino-pyridin-3-yl)-propenyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (90 mg, 0.21 mmol, higher Rf value) and 4-[3-(4-tert-butoxycarbonylamino-pyridin-3-yl)-allyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester_(0.24 g, 0.56 mmol, lower Rf value). For the former: MS m/z 433 (M+1); 1H NMR (CDCl3, 300 MHz) δ8.38 (d, 1H), 8.28 (s, 1H), 7.93 (d, 1H), 7.48 (d, 1H), 6.67 (s, 1H), 5.10 (m, 1H), 4.15 (s, 2H), 3.70 (t, 2H), 3,46 (t, 2H), 3.39 (d, 2H), 1.48 (s, 9H), 1.45 (s, 9H). For the latter: MS m/z 433 (M+1); 1H NMR (CDCl3, 300 MHz) δ8.39 (s, 1H), 8.37 (d, 1H), 7.98 (d, 1H), 6.77 (s, 1H), 6.52 (d, 1H), 6.07 (m, 1H), 4.23 (d, 2H), 4.12 (s, 2H), 3,69 (t, 2H), 3.40 (t, 2H), 1.52 (s, 9H), 1.45 (s, 9H).

Workup

  1. washwashed H2O (2×)
  2. concentrationThe CH2Cl2 layer is concentrated
  3. customthe residue is chromatographed (5% MeOH/CH2Cl2)
  4. customto give
  5. additiona mixture of two isomers (0.40 g, 0.92 mmol)
  6. customThe mixture is separated into its constituent isomers upon further chromatography (EtOAc)

Sources & evidence

ORD record
ord-a4c2f43942d54d8287ef4ae1ebe664cd
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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