2-azaspiro[4.4]nonane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate was dissolved in NMP (1 mL) and combined with 2-azaspiro[4.4]nonane (8.72 mg, 0.070 mmol) and N,N-diisopropylethylamine (27 mg, 0.21 mmol). This mixture was stirred at rt for 24 h. A 1M lithium hydroxide solution (0.348 mL, 0.348 mmol) was added to the reaction mixture and it was heated at 50° C. for 4 h to complete the ester hydrolysis. The reaction mixture was concentrated in vacuo and purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp) to give 11.1 mg (27% yield) of S)-2-(tert-butoxy)-2-(5-methyl-2-phenyl-7-(2-azaspiro[4.4]nonan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic (1:1 solvate with NMP) as a yellow waxy solid. was heated at 50° C. for 4 h The reaction mixture was concentrated in vacuo purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate was dissolved in NMP (1 mL) and combined with 2-azaspiro[4.4]nonane (8.72 mg, 0.070 mmol) and N,N-diisopropylethylamine (27 mg, 0.21 mmol). This mixture was stirred at rt for 24 h. A 1M lithium hydroxide solution (0.348 mL, 0.348 mmol) was added to the reaction mixture and it was heated at 50° C. for 4 h to complete the ester hydrolysis. The reaction mixture was concentrated in vacuo and purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp) to give 11.1 mg (27% yield) of S)-2-(tert-butoxy)-2-(5-methyl-2-phenyl-7-(2-azaspiro[4.4]nonan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic (1:1 solvate with NMP) as a yellow waxy solid. was heated at 50° C. for 4 h The reaction mixture was concentrated in vacuo purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]nonane (F); spiro[bicyclo[2.2.1]heptane-2,3'-pyrrolidine] (G); spiro[bicyclo[2.2.2]octane-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]-pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6a-hexahydrocyclopenta[b]pyrrole (O); all of which can optionally be substituted.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (S)-methyl 2-(tert-butoxy)-2-(7-chloro-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate was dissolved in NMP (1 mL) and combined with 2-azaspiro[4.4]nonane (8.72 mg, 0.070 mmol) and N,N-diisopropylethylamine (27 mg, 0.21 mmol). This mixture was stirred at rt for 24 h. A 1M lithium hydroxide solution (0.348 mL, 0.348 mmol) was added to the reaction mixture and it was heated at 50° C. for 4 h to complete the ester hydrolysis. The reaction mixture was concentrated in vacuo and purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp) to give 11.1 mg (27% yield) of S)-2-(tert-butoxy)-2-(5-methyl-2-phenyl-7-(2-azaspiro[4.4]nonan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic (1:1 solvate with NMP) as a yellow waxy solid. was heated at 50° C. for 4 h The reaction mixture was concentrated in vacuo purified by Biotage (4 g column, 0-10% MeOH/CH2Cl2 ramp)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]-nonane (F); spiro[(bicyclo[2.2.1]heptane)-2,3'-pyrrolidine] (G); spiro[(bicyclo[2.2.2]octane)-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6ahexahydrocyclopenta[b]pyrrole (O); pyrrolidine (P); indoline (Q) and thiazolidine (R), all of which can be optionally substituted.