Novel salt of (r)-(1-methylpyrrolidine-3-yl)methyl(3'-chloro-4'-fluoro-[1,1'-biphenyl]-2-yl)carbamate and crystal form thereof

A form I of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein an X-ray powder diffraction (XRPD) pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 13.402±0.2°, 14.300±0.2°, 18.519±0.2°, 19.577±0.2° and 21.499±0.2°.

A method for preparing the form I of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method comprises steps of:

• dissolving a free base of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate in acetone;
• inserting oxalic acid into the said solution and stirring the resulting mixture;
• and crystallizing the resulting mixture by means of methyl-t-butyl ether.

A form II of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 13.439±0.2°, 14.481±0.2°, 18.501±0.2°, 21.779±0.2° and 23.358±0.2°.

A form III of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 10.720±0.2°, 11.018±0.2°, 14.239±0.2°, 17.880±0.2° and 21.440±0.2°.

A form IV of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 16.642±0.2°, 17.839±0.2°, 20.981±0.2°, 21.580±0.2° and 22.701±0.2°.

A method for preparing the form IV of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method includes the step of recrystallizing the form I of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate by means of 1,4-dioxane.

A form V of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 10.925±0.2°, 14.200±0.2°, 20.559±0.2° and 21.396±0.2°.

A method for preparing the form V of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method comprises the step of recrystallizing the form II of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate by means of butanol.

A form VI of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 10.127±0.2°, 10.893±0.2°, 11.751±0.2° and 17.978±0.2°.

A method for preparing the form VI of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method comprises the step of recrystallizing the form II of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate by means of methanol.

A form VII of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 8.169±0.2°, 8.847±0.2°, 11.071±0.2° and 13.156±0.2°.

A method for preparing the form VII of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method comprises the step of recrystallizing the form II of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate by means of the recrystallization solvent selected from the group consisting of ethanol;

• benzene;
• and a mixture thereof.

A form VIII of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the XRPD pattern comprises at least three diffraction peaks selected from the group consisting of diffraction angles 2θ of 8.903±0.2°, 13.090±0.2°, 14.347±0.2° and 15.871±0.2°.

A method for preparing the form VIII of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate, wherein the method comprises the step of recrystallizing the form II of (R)-(1-methylpyrrolidine-3-yl)methyl(3′-chloro-4′-fluoro-[1,1′-biphenyl]-2-yl)carbamate oxalate by means of the recrystallization solvent selected from the group consisting of ethanol;

• benzene;
• and a mixture thereof.