N-propan-2-yl-1H-pyrrole-3-carboxamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: DIPEA (284 mg, 381 uL, 2.2 mmol) was added to a solution of 1H-pyrrole-3-carboxylic acid (111 g, 1.0 mmol) and isopropylamine (118 mg, 170 uL, 2.0 mmol) in DMF (10 mL) at 0° C. Stirring for 20 min, HATU (570 g, 1.5 mmol) was added at 0° C. The reaction mixture was stirred overnight at room temperature, diluted with EtOAc (100 mL), washed with H2O (3×10 mL) and dried over Na2SO4. The crude product was purified by MPLC using EtOAc on silica gel. Yield: 80 mg (52%). 1H NMR (400 MHz, CHLOROFORM-D) δ 1.19 (d, J=6.64 Hz, 6 H), 3.95-4.31 (m, 1 H), 6.52 (dd, J=2.93, 1.56 Hz, 1 H), 6.70 (dd, J=2.93, 2.15 Hz, 1 H), 7.31 (t, J=1.76 Hz, 1 H), 7.58 (s, 1 H). The reaction mixture was stirred overnight at room temperature washed with H2O (3×10 mL) dried over Na2SO4 The crude product was purified by MPLC

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

Procedure: Following the same procedure in Example 29, using N-isopropyl-1H-pyrrole-3-carboxamide (76 mg, 0.50 mmol) (see following step B for preparation), sodium hydride (159 mg, 60%, 3.97 mmol) and 2-(1,1-dimethylpropyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazole-5-sulfonyl chloride (535 mg, 1.39 mmol) in THF (15 mL). The crude product was purified by MPLC using Hex/EtOAc (3:7) on silica gel to give 158 mg (64%) of a white solid as the title compound. 1H NMR (400 MHz, METHANOL-D4) δ 0.77 (t, J=7.42 Hz, 3 H), 1.15 (d, J=6.64 Hz, 6 H), 1.39-1.56 (m, 4 H), 1.59 (s, 6 H), 1.94 (q, J=7.42 Hz, 2 H), 2.19-2.38 (m, 1 H), 3.23-3.35 (m, 2 H), 3.83-3.96 (m, 2 H), 4.01-4.15 (m, 1 H), 4.41 (d, J=7.62 Hz, 2 H), 6.67 (dd, J=3.32, 1.56 Hz, 1 H), 7.28 (dd, J=3.12, 2.34 Hz, 1 H), 7.79-7.86 (m, 1 H), 7.88-7.99 (m, 2 H) 8.26 (d, J=1.17 Hz, 1 H); MS (ESI) (M+H)+=501.3; Anal. Calcd for C26H36N4O4S+1.2 TFA+0.1H2O (615.50): C, 55.33; H, 6.11; N, 9.09. Found: C, 55.38; H, 6.16; N, 9.04. The crude product was purified by MPLC