1,2-Dichloroethane → 2,3-Dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide

HRID 885686Notes

Reaction equation

HRID 885686 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=O)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[CH3:14][O:15][C:16]1[N:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[C:19]2[N:26]1[CH:34]=[C:33]2[C:28]([CH2:29][CH2:30][CH:31]([NH2:35])[CH2:32]2)=[N:27]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.CO>[CH3:14][O:15][C:16]1[N:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[C:19]2[N:26]1[CH:34]=[C:33]2[C:28]([CH2:29][CH2:30][CH:31]([NH:35][C:11]([C:9]3[CH:8]=[CH:7][C:6]4[O:1][CH2:2][CH2:3][O:4][C:5]=4[CH:10]=3)=[O:13])[CH2:32]2)=[N:27]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 27588331,4-Benzodioxane-6-carboxylic AcidHCID 595606482-(6-Methoxy-[1,5]naphthyridin-4-yl)4,5,6,7-tetrahydro-2H-indazol-5-ylamine

Product 1

HCID 119485572,3-Dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amideYield 30.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid (44 mg, 0.24 mmol) and 2-(6-methoxy[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamine (48 mg, 0.16 mmol) in DMF (1 mL) was added HOBT (1-hydroxybenzotriazole; 33 mg, 0.24 mmol) and EDC; 47 mg, 0.24 mmol). The reaction mixture was stirred for 1.5 h at RT. The reaction mixture was diluted with CH3OH and purified directly by basic reverse phase HPLC to provide 22 mg (30%) of the title compound. MS (ESI): exact mass calculated for C25H23N5O4, 457.18; m/z found, 458.3 [M+H]+. 1H NMR (500 MHz, CDCl3): 9.14 (s, 1H), 8.76 (d, J=5.1, 1H), 8.25 (d, J=9.1, 1H), 8.16 (d, J=5.1, 1H), 7.31-7.28 (m, 1H), 7.26-7.23 (m, 1H), 7.17 (d, J=9.1, 1H), 6.86 (d, J=8.4, 1H), 6.13 (d, J=7.7, 1H), 4.54-4.51 (m, 1H), 4.27-4.24 (m, 4H), 4.07 (s, 3H), 3.19 (dd, J=15.5, 5.1, 1H), 2.99-2.96 (m, 2H), 2.66 (dd, J=15.5, 7.7, 1H), 2.21-2.16 (m, 1H), 2.10-2.03 (m, 1H).

Workup

  1. custompurified directly by basic reverse phase HPLC

Sources & evidence

ORD record
ord-72098dd074a54e839541b99b8f42caff
Source dataset
uspto-grants-2012_08
Patent number
US08242275B2

Reaction notes

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