tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylate → 4-(4-benzylphenylamino)-6-(2-(1-N-BOC-piperazin-4-yl)ethylamino)-1,7-naphthyridine-3-carbonitrile

HRID 2113565Notes

Reaction equation

HRID 2113565 reaction equation
[CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][N:21]=[C:22](F)[CH:23]=3)[N:18]=[CH:17][C:16]=2[C:26]#[N:27])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28]([N:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH2:42][NH2:43])[CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].FC1C=C2C(=NC=1)N=CC=C2.FC1C=CC2C(=NC=CC=2)N=1>C(Cl)Cl.CO.C1COCC1>[CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[C:24]3[C:19](=[CH:20][N:21]=[C:22]([NH:43][CH2:42][CH2:41][N:38]4[CH2:39][CH2:40][N:35]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:36][CH2:37]4)[CH:23]=3)[N:18]=[CH:17][C:16]=2[C:26]#[N:27])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1514400tert-Butyl 4-(2-aminoethyl)piperazine-1-carboxylateHCID 20531189HCID 20531189, compoundHCID 585467682-Fluoro-1,8-naphthyridineHCID 69185247HCID 69185247, compound

Product 1

HCID 691837124-(4-benzylphenylamino)-6-(2-(1-N-BOC-piperazin-4-yl)ethylamino)-1,7-naphthyridine-3-carbonitrileYield 23%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A microwave vial was charged with 4-(4-benzylphenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile (0.100 g, 0.282 mmol), 1-N-BOC-4-(2-aminoethyl)piperazine and 2 mL THF, crimp-sealed, and heated in a microwave reactor at 180° C. for 35 minutes, until TLC analysis (5% MeOH in CH2Cl2) showed disappearance of the 6-fluoronaphthyridine. This process was repeated with 3 additional aliquots of the fluoronaphthyridine (0.120 g, 0.100 g, 0.100 g), and the contents of all 4 vials were then combined, partitioned between 50 mL each EtOAc and brine, and worked up as described above for the synthesis of WAY-191220. The crude product was purified by flash chromatography over silica gel (5% MeOH in CH2Cl2) and lyophilized to give pure 4-(4-benzylphenylamino)-6-(2-(1-N-BOC-piperazin-4-yl)ethylamino)-1,7-naphthyridine-3-carbonitrile (0.151 g, 23% yield): 1H NMR (400 MHz, DMSO-D6) δ 1.39 (s, 9 H) 2.34-2.44 (m, 4 H) 2.57 (t, J=6.6 Hz, 2 H) 3.21-3.42 (m, 6 H) 3.99 (s, 2 H) 6.59 (t, J=5.3 Hz, 1 H) 7.03 (s, 1 H) 7.14-7.34 (m, 9 H) 8.22 (s, 1 H) 8.81 (s, 1 H) 9.56 (s, 1 H).

Workup

  1. customcrimp-sealed
  2. custompartitioned between 50 mL each EtOAc and brine
  3. customas described above for the synthesis of WAY-191220
  4. customThe crude product was purified by flash chromatography over silica gel (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-3cabb5c94809448d8e76e61cded7b693
Source dataset
uspto-grants-2008_10
Patent number
US07432279B2

Reaction notes

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