1,1-DICYCLOPROPANECARBOXYLIC ACID

Cap B-41 To a solution of ester B-41a (100 mg, 0.462 mmol) in a mixture of methanol (2.5 mL) and water (0.5 mL) at 0 °C was added aq. NaOH (IN) (1 mL, 0.247 mmol) and stirred for 10 min at 0 °C, warmed to 25 °C and stirred for 12 h. The volatile components were removed completely under reduced pressure. Water was added (5 mL) and extracted with diethyl ether (2 X 10 mL). The aqueous layer was acidified with 1.5 N HC1 (pH ~2) and extracted with 10percent MeOH / DCM (3x10 mL) mixture. The combined organic layer was washed with brine solution (10 mL) and dried over anhyd. NaScheme 3, step 2: (3-chloro-5, 6-dimethyl-pyrazin-2-yl)hydrazine (4.08 g, 23.6 mmol), l-cyclopropylcyclopropanecarboxylic acid (4.77 g, 37.8 mmol), HATU (14.7 g, 37.9 mmol) and DIPEA (14.4 mL, 82.6 mmol) are dissolved in DCM (120 ml) and stirred at room temperature for 45 minutes. The reaction mixture is washed with water, dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by flash chromatography on silica, eluting with 0-100% EtOAc in hexanes to give the title compound (4.37 g, 65.8%). MS (m/z) 280 (M+H).Scheme 1, step 4: l-cyclopropylcyclopropanecarboxylic acid (10.13 g, 80.28 mmol) is added to a stirred solution of 5-chloro-l-(cyclopropylmethyl)-3-hydrazino-6-methylpyrazin-2-one (16.69 g, 72.98 mmol) and DIPEA (42.00 mL, 240.8 mmol) in dry DMF (417.3 mL) under a N2 atmosphere at room temperature followed by the addition of N-[(5-chloro-3-oxido-1H-benzotriazol-l-yl)-4-morpholinylmethylene]-N-methylmethanaminium hexafluorophosphate (36.59 g, 80.28 mmol). The reaction mixture is stirred at room temperature for 2 hours. Water (1.4 L) is added to the reaction mixture and a precipitate forms. The reaction mixture is filtered and the isolated solid is washed with Et20 (1 L) to give the title compound (16.06 g, 65%). MS (m/z) 339 (M+H).Add TEA (0.22 mL, 1.6 mmol) to a suspension of 4-(cyclopropylmethyl)-2-hydrazino-6, 7, 8, 9-tetrahydro-5H-cyclohepta[b]pyrazin-3 -one (112 mg, 0.4 mmol), Cool a solution of Dissolve 1 -(cyclobutylmethyl)-3 -hydrazino-7, 8-dihydro-5H- pyrano[3 , 4-b]pyrazin-2-one (275 mg, 0.9 mmol), 1 -cyclopropylcyclopropanecarboxylicacid (178 mg, 1.4 mmol), HOBT (206 mg, 1.5 mmol), EDCI (286 mg, 1.5 mmol) and TEA (433 1iL, 3.1 mmol) in DMF (4 mL). Stir the mixture at RT overnight. Dilute with water and extract with EtOAc. Wash the combined organic extracts with 10% aqueous LiC1 followed by saturated aqueous NaC1, dry over anhydrous Mg504, filter, concentrate under reduced pressure, and dry under vacuum overnight to give the crude title compound(334 mg, 85%) sufficient for use without additional purification. ES/MS (m/z): 359 (M+H).Dissolve 1-butyl-3-hydrazino-7, 8-dihydro-5H-pyrano[3, 4-b]pyrazin-2-one (694 mg, 2.9 mmol), Dissolve 1 -(cyclopropylmethyl)-3 -hydrazino-7, 8-dihydro-5H- pyrano[3 , 4-b]pyrazin-2-one (475 mg, 1.7 mmol), 1 -cyclopropylcyclopropanecarboxylicacid (316 mg, 2.5 mmol), HOBT (368 mg, 2.6 mmol), and EDCI (512 mg, 2.7 mmol) in DMF (4 mL) containing TEA(774 tL, 5.6 mmol). Stir the reaction at RT for 2 hr. Dilute with water and extract with EtOAc. Wash the extracts with 10% aqueous LiC1 followed by saturated aqueous NaC1, dry over anhydrous Mg504, filter, and concentrate under reduced pressure to give the crude title compound (585 mg, 71% yield). ES/MS (m/z):345 (M+H).A mixture of

Molecular Weight:126.15
XLogP3:1.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:126.068079557
Monoisotopic Mass:126.068079557
Topological Polar Surface Area:37.3
Heavy Atom Count:9
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes