1,2-Dichloroethane → 1-(2-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-2-hydroxyethanone

HRID 2200071Notes

Reaction equation

HRID 2200071 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:23]5[CH2:22][NH:21][CH2:20][CH2:19][C:18]=5[N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:26]=[CH:27][N:28]=[CH:29][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:30][CH2:31][C:32](O)=[O:33].C(Cl)CCl.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:23]5[CH2:22][N:21]([C:31](=[O:30])[CH2:32][OH:33])[CH2:20][CH2:19][C:18]=5[N:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:26]=[CH:27][N:28]=[CH:29][C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 665496459-cyclopentyl-N-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

Product 1

HCID 665496441-(2-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-2-hydroxyethanoneYield 71.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 9-cyclopentyl-N-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-yl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine (21) (145 mg, 0.367 mmol) in DMF (10 mL) were added 2-hydroxyacetic acid (34.3 mg, 0.451 mmol), EDC (191.7 mg, 0.451 mmol), N-hydroxybenzotriazole (61 mg, 0.451 mmol), and N,N-diisopropylethylamine (157 uL, 0.903 mmol). The mixture thus obtained was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and the residue was purified by flash chromatography on silica gel eluting with 20% to 75% solvent A (DCM:MeOH:NH4OH, 100:10:1) to give the title compound as an off-white solid (117 mg, 70% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.77-1.80 (2H, m), 2.07-2.10 (4H, m), 2.42-2.44 (2H, m), 2.82-2.91 (2H, m), 3.66-3.82 (2H, m), 4.18-4.20 (2H, m), 4.57-4.66 (2H, m), 5.36 (1H, m), 7.68 (1H, d, J=10.0 Hz), 8.06 (1H, d, J=5.0 Hz), 8.19 (1H, d, J=10.0 Hz), 8.48 (1H, d, J=5.0 Hz), 9.03 (1H, s), 9.31 (1H, s) 9.98 (1H, br. s) ppm; LCMS m/z: 444 (M+1).

Workup

  1. customThe mixture thus obtained
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified by flash chromatography on silica gel eluting with 20% to 75% solvent A (DCM:MeOH:NH4OH, 100:10:1)

Sources & evidence

ORD record
ord-5baa5b6b2e094b3c83c64c8168ea1d18
Source dataset
uspto-grants-2016_06
Patent number
US09359355B2

Reaction notes

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