methyl 2-amino-2-(oxetan-3-yl)acetate

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

Procedure: (N—((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)-2-(3,5-dichlorophenylamino)-2-(oxetan-3-yl)acetamide). To a solution of 2-amino-2-(oxetan-3-yl)acetic acid (0.3 mmol) and (R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine (0.3 mmol) in DMF (2 mL) was added DIEA (0.9 mmol), EDCI (0.33 mmol), and HOBt (0.33 mmol). The resulting solution was then stirred at rt for 1 h. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA to afford the title compound. 1H NMR (400 MHz, MeOD) δ 8.08 (s, 1H), 7.03 (d, J=3.51 Hz, 1H), 6.55 (d, J=3.51 Hz, 1H), 6.41 (t, J=1.76 Hz, 1H), 6.37 (d, J=1.76 Hz, 1H), 4.64-4.69 (m, 1H), 4.54-4.60 (m, 1H), 4.42 (t, J=6.27 Hz, 1H), 4.07 (d, J=9.29 Hz, 1H), 3.71-3.97 (m, 3H), 1.83-1.93 (m, 1H), 1.76 (br. s., 1H), 1.62 (br. s., 1H). EIMS (m/z): calcd. for C22H24Cl2N6O2(M+1H) 475. found 475. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA

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

Procedure: (N—((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)-2-(3,5-dichlorophenylamino)-2-(oxetan-3-yl)acetamide). To a solution of 2-amino-2-(oxetan-3-yl)acetic acid (0.3 mmol) and (R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine (0.3 mmol) in DMF (2 mL) was added DIEA (0.9 mmol), EDCI (0.33 mmol), and HOBt (0.33 mmol). The resulting solution was then stirred at rt for 1 h. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA to afford the title compound. 1H NMR (400 MHz, MeOD) δ 8.08 (s, 1H), 7.03 (d, J=3.51 Hz, 1H), 6.55 (d, J=3.51 Hz, 1H), 6.41 (t, J=1.76 Hz, 1H), 6.37 (d, J=1.76 Hz, 1H), 4.64-4.69 (m, 1H), 4.54-4.60 (m, 1H), 4.42 (t, J=6.27 Hz, 1H), 4.07 (d, J=9.29 Hz, 1H), 3.71-3.97 (m, 3H), 1.83-1.93 (m, 1H), 1.76 (br. s., 1H), 1.62 (br. s., 1H). EIMS (m/z): calcd. for C22H24Cl2N6O2(M+1H) 475. found 475. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA

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

Procedure: (N—((R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)-2-(3,5-dichlorophenylamino)-2-(oxetan-3-yl)acetamide). To a solution of 2-amino-2-(oxetan-3-yl)acetic acid (0.3 mmol) and (R)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-amine (0.3 mmol) in DMF (2 mL) was added DIEA (0.9 mmol), EDCI (0.33 mmol), and HOBt (0.33 mmol). The resulting solution was then stirred at rt for 1 h. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA to afford the title compound. 1H NMR (400 MHz, MeOD) δ 8.08 (s, 1H), 7.03 (d, J=3.51 Hz, 1H), 6.55 (d, J=3.51 Hz, 1H), 6.41 (t, J=1.76 Hz, 1H), 6.37 (d, J=1.76 Hz, 1H), 4.64-4.69 (m, 1H), 4.54-4.60 (m, 1H), 4.42 (t, J=6.27 Hz, 1H), 4.07 (d, J=9.29 Hz, 1H), 3.71-3.97 (m, 3H), 1.83-1.93 (m, 1H), 1.76 (br. s., 1H), 1.62 (br. s., 1H). EIMS (m/z): calcd. for C22H24Cl2N6O2(M+1H) 475. found 475. The solvent was removed in vacuo to afford a residue, which was purified by reverse phase chromatography C18 column and 10% acetonitrile/water containing 0.1% TFA