Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:3]=1.[CH2:21]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)[CH:22]=[CH2:23]>CS(C)=O.O>[CH2:21]([N:24]1[CH2:29][CH2:28][N:27]([C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH:8][S:9]([C:12]3[CH:17]=[CH:16][C:15]([CH:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=3)(=[O:11])=[O:10])[CH:3]=2)[CH2:26][CH2:25]1)[CH:22]=[CH2:23]
Reactant: C=CCN1CCNCC1
Reactant: CC(C)c1ccc(S(=O)(=O)Nc2cc(Cl)ncn2)cc1
Solvent: O
Solvent: CS(C)=O
Product: C=CCN1CCN(c2cc(NS(=O)(=O)c3ccc(C(C)C)cc3)ncn2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
430 mg (1.38 mmol) of N-(6-chloropyrimidin-4-yl)-4-isopropylbenzenesulfonamide from Example 18.1 were dissolved in 3 ml of dimethyl sulfoxide, after which 1.74 g (13.79 mmol) of N-allylpiperazine were added and the mixture was stirred overnight. Subsequently, the reaction mixture was stirred at 100° C., in a microwave oven, for 45 minutes. After the reaction mixture had cooled down to room temperature, it was diluted with 50 ml of water. After that, the aqueous reaction mixture was extracted with 50 ml of ethyl acetate and the precipitate was filtered off with suction, with 190 mg (34% of theory) of the title compound being obtained.
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([C:15](=[O:18])[NH:16][N:17]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:7]=1.[S:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[NH:28][CH2:29][CH2:30][NH2:31].C(N(CC)CC)C>C1COCC1>[S:19]1[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[N:21]=[C:20]1[NH:28][CH2:29][CH2:30][NH:31][C:2]1[C:3]2[N:4]([C:15](=[O:18])[NH:16][N:17]=2)[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:7]=1
Reactant: NCCNc1nc2ccccc2s1
Reactant: O=c1[nH]nc2c(Br)nc(-c3ccc(Cl)cc3)cn12
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=c1[nH]nc2c(NCCNc3nc4ccccc4s3)nc(-c3ccc(Cl)cc3)cn12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 50 mg of the product of Step A, 43 mg of N1-benzothiazol-2-yl-ethane-1,2-diamine, and 124 mg of triethylamine in THF (1.0 mL) was heated to reflux. After 16 h, the reaction mixture was cooled to ambient temperature and then partitioned between EtOAc and water. The organic layer was dried over sodium sulfate, filtered, and concentrated to a residue that was purified by silica gel chromatography to afford the title compound as a white solid. MS (M+H+)=438.3.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[CH2:19]([C:23]1[O:24][C:25]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:26]([C:28](O)=[O:29])[N:27]=1)[CH2:20][CH2:21][CH3:22]>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:28]([C:26]3[N:27]=[C:23]([CH2:19][CH2:20][CH2:21][CH3:22])[O:24][C:25]=3[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[O:29])=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Reactant: CCCCc1nc(C(=O)O)c(-c2ccccc2)o1
Product: CCCCc1nc(C(=O)Nc2ccn(Cc3ccc(C(C)=O)o3)n2)c(-c2ccccc2)o1

Procedure:
Following general procedure B followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and 2-butyl-5-phenyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=1.11 min; [M+H]+=433.37.
Reaction SMILES: [CH:1]1([C@@:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([C:9]2[N:13]=[CH:12][NH:11][N:10]=2)[OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[C:31]([O:30][C:28]([N:25]1[CH2:26][CH2:27][CH:22]([CH2:21][N:11]2[CH:12]=[N:13][C:9]([C@:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)([OH:8])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:10]2)[CH2:23][CH2:24]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]
Reactant: O[C@](c1ccccc1)(c1nc[nH]n1)C1CCCCC1
Reactant: CC(C)(C)OC(=O)N1CCC(CBr)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(Cn2cnc([C@](O)(c3ccccc3)C3CCCCC3)n2)CC1
Temperature: 70 °C
Reaction time: 5 h
Yield: 64 %

Procedure:
(R)-cyclohexyl(phenyl)1H-1,2,4-triazol-3-ylmethanol (Preparation 2, 3.0 g, 11.7 mmol) was dissolved in acetone (60 mL) and tert-butyl 4-(bromomethyl)piperidine-1-carboxylate (3.24 g, 11.7 mmol) added, followed by cesium carbonate (7.60 g, 23.3 mmol). After stirring at 70° C. for 5 hours, the reaction was allowed to cool to room temperature and stirred for a further 16 hours. The solvent was removed in vacuo, and the residue partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. 100 mg of this residue was dissolved in acetonitrile (0.5 ml) and left to evaporate, almost to dryness, at which point the resulting oil began to crystallise. The remainder of the residue was dissolved in acetonitrile (55 ml) and seeded with the crystalline material obtained above. Crystallisation was allowed to occur over 18 hours and the resulting solid collected by filtration to furnish the title compound as a white solid, in 64% yield, 3.4 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[N:14]=[C:15]([NH2:18])[O:16][CH:17]=1.C(N(CC)CC)C.[C:26](Cl)(=[O:28])[CH3:27]>ClCCl>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:13]1[N:14]=[C:15]([NH:18][C:26](=[O:28])[CH3:27])[O:16][CH:17]=1
Reactant: CC(=O)Cl
Reactant: COc1ccc2ccccc2c1-c1coc(N)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc2ccccc2c1-c1coc(NC(C)=O)n1
Temperature: 25 °C
Yield: 36 %

Procedure:
To a solution of 4-(2-methoxy-naphthalen-1-yl)-oxazol-2-ylamine (17, 450 mg), triethylamine (0.78 mL) and dichloromethane (5 mL) at 0° C. was added acetyl chloride (0.2 mL). The solution was allowed to warm to room temperature overnight and the reaction was quenched by the addition of a mixture of dichloromethane and methanol. The solution was washed with brine (×2), dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography, eluting with 2% methanol in dichloromethane, to afford N-[4-(2-methoxy-naphthalen-1-yl)-oxazol-2-yl]-acetamide (25) (190 mg, 36%) as an off-white solid. 1H NMR (DMSO-D6): 2.1 (3H, br s), 3.9 (3H, s), 7.2 (1H, s), 7.35-7.40 (1H, m), 7.45-7.50 (1H, m), 7.55 (1H, d, J=9.2 Hz), 7.90-7.95 (2H, m), 8.05 (1H, d, J=9.2 Hz), 11.2 (1H, br s). Mass Spectrum (m/z): 283 (M+H)+.
Reaction SMILES: O1CCCOB1[C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].Br[C:16]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:17]=1[NH2:18].C([O-])([O-])=O.[K+].[K+].C1(C)C=CC=CC=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[C:23]([C:21]1[CH:22]=[CH:16][C:17]2[C:19](=[C:7]3[C:8](=[C:9]([NH2:10])[N:18]=2)[CH:11]=[CH:12][CH:13]=[CH:14]3)[CH:20]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)c1ccc(N)c(Br)c1
Reactant: N#Cc1ccccc1B1OCCCO1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CC(C)(C)c1ccc2nc(N)c3ccccc3c2c1
Yield: 35.4 %

Procedure:
35.7 g (190 mmol) 2-(1,3,2-dioxaborinan-2-yl)benzonitrile, 31.9 g (158 mmol) 2-bromo-4-(tertbutyl)aniline, 3.6 g (3.16 mmol) tetrakis(triphenylphosphine)palladium(0) and 59.0 g (427 mmol) K2CO3 were heated to reflux in a 2 L flask containing 400 ml toluene and 300 mL ethanol. The reaction mixture was heated for 19 hours under constant N2 purge. HPLC of the reaction mixture indicated consumption of the starting aniline. The mixture was cooled and then filtered to remove the base. The base was washed with EtOAc to remove trace organic. The combined filtrate was evaporated down to give impure oil. The oil was purified on a column of silica using 95/5/0.05 CH2Cl2/MeOH/NH4OH as eluent to obtain separation. The product fractions were evaporated of solvent and the resultant residue recrystallized from CH2Cl2/hexanes to yield 14.0 g of the target compound as white solids (35.5% yield, confirmed by GC-MS).
Reaction SMILES: Br[C:2]1[N:3]=[CH:4][N:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[C:15]([O:23][CH2:24][CH3:25])[CH:14]=3)[CH:10]=[C:9]([C:26]([F:29])([F:28])[F:27])[N:8]=2)[CH:6]=1.[NH2:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1>>[CH2:24]([O:23][C:15]1[CH:14]=[C:13]([C:11]2[CH:10]=[C:9]([C:26]([F:29])([F:28])[F:27])[N:8]=[C:7]([N:5]3[CH:6]=[C:2]([C:34]4[CH:35]=[CH:36][C:31]([NH2:30])=[N:32][CH:33]=4)[N:3]=[CH:4]3)[N:12]=2)[CH:18]=[CH:17][C:16]=1[C:19]([F:22])([F:21])[F:20])[CH3:25]
Reactant: CCOc1cc(-c2cc(C(F)(F)F)nc(-n3cnc(Br)c3)n2)ccc1C(F)(F)F
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: CCOc1cc(-c2cc(C(F)(F)F)nc(-n3cnc(-c4ccc(N)nc4)c3)n2)ccc1C(F)(F)F

Procedure:
The title compound was prepared from 2-(4-bromo-imidazol-1-yl)-4-(3-ethoxy-4-trifluoromethyl-phenyl)-6-trifluoromethyl-pyrimidine (example E.9) (0.24 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.65 mmol) according to the general procedure VI. Obtained as a yellow solid (0.038 g, 15%). MS (ISP) 495.3 [(M+H)+]; mp 266.5° C.
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([O:27]C)=[O:26])=[CH:12][C:13]=3[N:14]3[C:20]=2[C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[NH:17][CH2:16][CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C1COCC1.CO.[OH-].[Na+]>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([OH:27])=[O:26])=[CH:12][C:13]=3[N:14]3[C:20]=2[C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[NH:17][CH2:16][CH2:15]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCNc1ccccc1-3
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1ccc2c(C3CCCCC3)c3n(c2c1)CCNc1ccccc1-3
Yield: 76.7 %

Procedure:
A solution of methyl 13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-carboxylate (45.8 mg, 0.12 mmol) in THF/MeOH (1:2, 3 mL) and 1N aqueous NaOH (0.5 mL) was heated at 50° C. for 5 h. The reaction solution was concentrated to remove volatile organics, neutralized with TFA (0.04 mL) and purified by preparative HPLC (MeOH/H2O with TFA buffer) to yield 13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-carboxylic acid (33 mg, 0.092 mmol, 76%) as white solid. 1HNMR (500 MHz, MeOD) δ 8.25 (s, 1H), 7.96 (d, J=8.5 Hz, 1H), 7.79 (dd, J=8.5, 1.2 Hz, 1H), 7.63-7.52 (m, 3H), 7.50-7.46 (m, 1H), 4.44 (br s, 2H), 3.92-3.86 (m, 2H), 3.03 (tt, J=12.4, 3.1 Hz, 1H), 2.21-2.10 (m, 2H), 1.97-1.80 (m, 5H), 1.54-1.36 (m, 2H). LCMS: m/e 361 (M+H)+, ret time 1.88 min, column C, 2 minute gradient, start at 0% B.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[N:3]=1.[CH3:19][C:20]1[C:21]([CH2:26][OH:27])=[N:22][CH:23]=[CH:24][CH:25]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([C:13]2[O:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[C:5]([C:11]#[N:12])=[C:6]([O:27][CH2:26][C:21]2[C:20]([CH3:19])=[CH:25][CH:24]=[CH:23][N:22]=2)[N:7]=1
Reactant: Cc1cccnc1CO
Reactant: Cc1ccc(-c2nc(N)nc(S(C)=O)c2C#N)o1
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1ccc(-c2nc(N)nc(OCc3ncccc3C)c2C#N)o1

Procedure:
From 2-amino-4-methanesulfinyl-6-(5-methyl-furan-2-yl)-pyrimidine-5-carbonitrile, 3-methyl-2-pyridinemethanol and DBU in DME. ES-MS m/e (%): 322 (M+H+, 100).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:22]4[C:21]([CH3:23])=[C:20]([CH3:24])[N:19]=[C:18]([N:25](CC5C=CC(OC)=CC=5)CC5C=CC(OC)=CC=5)[C:17]=4[N:16]=[C:15]3[CH2:44][CH2:45][CH3:46])[O:10][N:9]=2)=[CH:4][CH:3]=1>FC(F)(F)C(O)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:22]4[C:21]([CH3:23])=[C:20]([CH3:24])[N:19]=[C:18]([NH2:25])[C:17]=4[N:16]=[C:15]3[CH2:44][CH2:45][CH3:46])[O:10][N:9]=2)=[CH:6][CH:7]=1
Reactant: CCCc1nc2c(N(Cc3ccc(OC)cc3)Cc3ccc(OC)cc3)nc(C)c(C)c2n1Cc1cc(-c2ccc(F)cc2)no1
Solvent: O=C(O)C(F)(F)F
Product: CCCc1nc2c(N)nc(C)c(C)c2n1Cc1cc(-c2ccc(F)cc2)no1
Yield: 34.2 %

Procedure:
Under a nitrogen atmosphere, a solution of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N,N-bis(4-methoxybenzyl)-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-4-amine (2.62 g, 4.23 mmol) in trifluoroacetic acid (25 mL) was stirred at room temperature for 2.7 days. The solution was then worked-up and the product isolated and purified as described in Part B of Example 21 to provide 0.549 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7-dimethyl-2-propyl-1H-imidazo[4,5-c]pyridin-4-amine as a white powder, mp 227.0-229.0° C.
Reaction SMILES: [CH:1]1([C:5]2[CH:10]=[CH:9][C:8]([C:11]3[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=3)=[C:7]([F:18])[C:6]=2[O:19][CH2:20][CH:21]2[CH2:23][O:22]2)[CH2:4][CH2:3][CH2:2]1.[NH3:24]>CO>[NH2:24][CH2:23][CH:21]([OH:22])[CH2:20][O:19][C:6]1[C:5]([CH:1]2[CH2:2][CH2:3][CH2:4]2)=[CH:10][CH:9]=[C:8]([C:11]2[CH:16]=[N:15][C:14]([NH2:17])=[CH:13][N:12]=2)[C:7]=1[F:18]
Reactant: N
Reactant: Nc1cnc(-c2ccc(C3CCC3)c(OCC3CO3)c2F)cn1
Solvent: CO
Product: NCC(O)COc1c(C2CCC2)ccc(-c2cnc(N)cn2)c1F
Temperature: 60 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
A mixture of 5-(4-cyclobutyl-2-fluoro-3-(oxiran-2-ylmethoxy)phenyl)pyrazin-2-amine (500 mg, 1.59 mmol) and 6 N NH3 in MeOH (5 mL) was stirred in a sealed tube at 60° Celsius for approximately 8 hours before cooling to rt and concentrating to dryness to give 1-amino-3-(3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenoxy)propan-2-ol (510 mg, 96%).
Reaction SMILES: C([O:5][C:6](=[O:54])[C:7]([O:10]/[N:11]=[C:12](/[C:41]1[N:42]=[C:43]([NH:46]C(OC(C)(C)C)=O)[S:44][CH:45]=1)\[C:13]([NH:15][C@@H:16]1[C:19](=[O:20])[N:18]([S:21]([OH:24])(=[O:23])=[O:22])[C@@H:17]1[CH2:25][N:26]1[CH2:30][C@@H:29]([CH2:31][NH:32]C(OC(C)(C)C)=O)[O:28][C:27]1=[O:40])=[O:14])([CH3:9])[CH3:8])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:32][CH2:31][C@H:29]1[O:28][C:27](=[O:40])[N:26]([CH2:25][C@@H:17]2[C@H:16]([NH:15][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([OH:54])=[O:5])/[C:41]3[N:42]=[C:43]([NH2:46])[S:44][CH:45]=3)[C:19](=[O:20])[N:18]2[S:21]([OH:24])(=[O:22])=[O:23])[CH2:30]1
Reactant: CC(C)(C)OC(=O)NC[C@@H]1CN(C[C@@H]2[C@H](NC(=O)/C(=N\OC(C)(C)C(=O)OC(C)(C)C)c3csc(NC(=O)OC(C)(C)C)n3)C(=O)N2S(=O)(=O)O)C(=O)O1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(O/N=C(\C(=O)N[C@@H]1C(=O)N(S(=O)(=O)O)[C@@H]1CN1C[C@@H](CN)OC1=O)c1csc(N)n1)C(=O)O
Yield: 78.5 %

Procedure:
Followed the general procedure for the acid mediated deprotection using (2R,3S)-3-((Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetamido)-2-(((R)-5-(((tert-butoxycarbonyl)amino)methyl)-2-oxooxazolidin-3-yl)methyl)-4-oxoazetidine-1-sulfonic acid (160 mg, 0.199 mmol), DCM (1.5 mL) and TFA (500 μL, 6.49 mmol). The crude residue purified by reverse phase prep HPLC (XSelect CSH, 30×100 mm, 5 μm, C18 column; ACN-water with 0.1% formic acid modifier, 60 mL/min), affording the title compound (85.8 mg, 78%) as a white powder. LCMS: m/z=548.0 (M+1); 1H NMR (400 MHz, D2O) δ ppm 6.93 (s, 1H), 5.23 (d, J=5.6 Hz, 1H), 4.76-4.69 (m, 1H), 4.54-4.49 (m, 1H), 3.84 (t, J=9.6 Hz, 1H), 3.56 (dd, J=14.8, 9.6 Hz, 1H), 3.41-3.34 (m, 2H), 3.21-3.11 (m, 2H), 1.34 (s, 3H), 1.32 (s, 3H).
Reaction SMILES: C([N:8](C(OC(C)(C)C)=O)[C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:24])=[N:18][C:19]=3[Cl:23])[C@H:11]([OH:25])[C@@H:10]1[OH:26])(OC(C)(C)C)=O.[CH2:34]([C:36]1[N:37]=[N:38]N[N:40]=1)[CH3:35]>>[Cl:24][C:17]1[N:16]=[C:15]2[C:20]([N:21]=[CH:22][N:14]2[C@@H:12]2[CH2:13][C@H:9]([N:8]3[N:38]=[N:37][C:36]([CH2:34][CH3:35])=[N:40]3)[C@@H:10]([OH:26])[C@H:11]2[OH:25])=[C:19]([Cl:23])[N:18]=1
Reactant: CCc1nn[nH]n1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@H]1C[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](O)[C@@H]1O
Product: CCc1nnn([C@H]2C[C@@H](n3cnc4c(Cl)nc(Cl)nc43)[C@H](O)[C@@H]2O)n1

Procedure:
This compound is prepared analogously to (1S,2R,3S,5R)-3-(di-Boc-amino)-5-(2,6-dichloro-purin-9-yl)-cyclopentane-1,2-diol (Step AA4) by replacing di-t-butyliminodicarboxylate (Step AA3) with 5-ethyl-2H-tetrazole.
Reaction SMILES: [CH3:1][N:2]([CH3:14])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[O:11][C:10]([CH2:12][OH:13])=[CH:9][CH:8]=1.[C:15](OC(=O)C)(=[O:17])[CH3:16].C([O-])(=O)C.[Na+]>C1C=CC=CC=1.O>[C:15]([O:13][CH2:12][C:10]1[O:11][C:7]([CH2:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:14])=[CH:8][CH:9]=1)(=[O:17])[CH3:16]
Reactant: CC(=O)OC(C)=O
Reactant: CN(C)CCCCc1ccc(CO)o1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccccc1
Product: CC(=O)OCc1ccc(CCCCN(C)C)o1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of 5-[4-(dimethylamino)butyl]-2-furanmethanol (4.9 g), acetic anhydride (25 g) and fused and powdered sodium acetate (10 g) in benzene (25 ml) was stirred at room temperature for 24 hr. The reaction was diluted with water (100 ml) and extracted with ethyl acetate. The combined extracts were distilled to afford a clear colourless oil b.p. 100°, 0.5 mm Hg. Found: C, 65.62; H, 9.03; N, 5.95. Calc. for C13H21NO3 : C, 65.24; H, 8.85; N, 5.85%.
Reaction SMILES: CO[C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:5][CH:4]=1.[CH3:31]C1C=CC(C=O)=CC=1>>[CH3:31][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:5][CH:4]=1
Reactant: Cc1ccc(C=O)cc1
Reactant: COc1ccc(CNCCNC(=O)c2sccc2Nc2ccnc3[nH]ccc23)cc1
Product: Cc1ccc(CNCCNC(=O)c2sccc2Nc2ccnc3[nH]ccc23)cc1

Procedure:
This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid [2-(4-methoxy-benzylamino)-ethyl]amide using 4-methylbenzaldehyde instead of 4-methoxy benzaldehyde. LCMS (ESI) 406 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.43-11.53 (1H, m) 10.24 (1H, s) 7.95-8.04 (1H, m) 7.75 (1H, d, J=5.47 Hz) 7.44 (1H, d, J=5.47 Hz) 7.25-7.31 (1H, m) 7.14 (1H, d, J=8.00 Hz) 7.03 (1H, d, J=7.81 Hz) 6.77 (1H, d, J=5.47 Hz) 6.41 (1H, dd, J=3.42, 1.85 Hz) 3.60 (2H, s) 3.31-3.36 (2H, m) 2.58 (2H, t, J=6.54 Hz) 2.22 (3H, s)
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:25](=[O:26])[N:6]2[C@@H:7]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)=[O:13])[C:8](=O)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[C:27]([C:30]1[N:37]2[C:33]([S:34][C:35]([Sn](CCCC)(CCCC)CCCC)=[CH:36]2)=[C:32]([C:51]([C:53]2[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=2)=[O:52])[N:31]=1)(=[O:29])[NH2:28]>>[C:27]([C:30]1[N:37]2[C:33]([S:34][C:35]([C:8]3[C@H:9]([CH3:10])[C@@H:5]4[C@@H:4]([C@H:2]([OH:1])[CH3:3])[C:25](=[O:26])[N:6]4[C:7]=3[C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=3)=[O:13])=[CH:36]2)=[C:32]([C:51]([C:53]2[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=2)=[O:52])[N:31]=1)(=[O:29])[NH2:28]
Reactant: C[C@@H](O)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Reactant: CCCC[Sn](CCCC)(CCCC)c1cn2c(C(N)=O)nc(C(=O)c3cccnc3)c2s1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4c(C(N)=O)nc(C(=O)c5cccnc5)c4s3)[C@H](C)[C@H]12
Yield: 66.9 %

Procedure:
4-Nitrobenzyl (1S,5R,6S)-2-[5-carbamoyl-7-(pyridin-3-yl)carbonylimidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (239 mg) was prepared in the same manner as in step a) of Example 1, except that 210 mg of 4-nitrobenzyl (1R,3R,5R,6S)-6-((1R)-1-hydroxyethyl)-1-methyl-2-oxo-1-carbapenam-3-carboxylate and 342 mg of 5-carbamoyl-7-(pyridin-3-yl)carbonyl-2-(tri-n-butylstannyl)imidazo[5,1-b]thiazole were used as the starting compounds.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]#[CH:14])[C:5](Cl)=[O:6].[CH:15]1([C@@H:21]([NH2:23])[CH3:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.C(N(CC)CC)C>C(OCC)(=O)C>[CH:15]1([C@@H:21]([NH:23][C:5](=[O:6])[C:4]2[CH:8]=[CH:9][C:10]([O:11][CH2:12][C:13]#[CH:14])=[C:2]([F:1])[CH:3]=2)[CH3:22])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: C#CCOc1ccc(C(=O)Cl)cc1F
Reactant: C[C@H](N)C1CCCCC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: C#CCOc1ccc(C(=O)N[C@@H](C)C2CCCCC2)cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.4 %

Procedure:
To a mixture of 5 ml of ethyl acetate and 0.30 g of 3-fluoro-4-(2-propynyloxy)benzoyl chloride were added 0.22 g of (1S)-1-(cyclohexyl)ethylamine and 0.20 g of triethylamine in order at room temperature. The mixture obtained was stirred at room temperature for 1 hour. Then, ethyl acetate was added to the reaction mixture and the mixture was filtered through Celite. The filtrate was concentrated under reduced pressure. The residue was washed with hexane to obtain 0.37 g of N-((1S)-1-cyclohexylethyl)-3-fluoro-4-(2-propynyloxy)benzamide (hereinafter, described as the compound 37 of the present invention) represented by the formula:
Reaction SMILES: [CH3:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH2:12][CH3:13])[N:7]([CH2:14][C:15]3[CH:32]=[CH:31][C:18]4/[C:19](=[CH:28]/[C:29]#[N:30])/[C:20]5[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=5[CH2:22][CH2:23][C:17]=4[CH:16]=3)[C:6]=2[CH:5]=[C:4]([C:33]([NH:35][NH2:36])=[O:34])[CH:3]=1.[CH:37](OCC)(OCC)OCC.O.N>C(O)(=O)C>[CH3:1][C:2]1[C:10]2[N:9]=[C:8]([CH2:11][CH2:12][CH3:13])[N:7]([CH2:14][C:15]3[CH:32]=[CH:31][C:18]4/[C:19](=[CH:28]/[C:29]#[N:30])/[C:20]5[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=5[CH2:22][CH2:23][C:17]=4[CH:16]=3)[C:6]=2[CH:5]=[C:4]([C:33]2[O:34][CH:37]=[N:36][N:35]=2)[CH:3]=1
Reactant: CCOC(OCC)OCC
Reactant: CCCc1nc2c(C)cc(C(=O)NN)cc2n1Cc1ccc2c(c1)CCc1ccccc1/C2=C\C#N
Agent: N
Solvent: O
Solvent: CC(=O)O
Product: CCCc1nc2c(C)cc(-c3nnco3)cc2n1Cc1ccc2c(c1)CCc1ccccc1/C2=C\C#N
Temperature: 50 °C
Reaction time: 6 h
Yield: 58 %

Procedure:
[step 2] (E)-{2-[4-Methyl-6-(hydrazinocarbonyl)-2-propylbenzimidazol-1-yl]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene}acetonitrile (40 mg, 0.08 mmol) obtained in step 1 was suspended in acetic acid (3 mL), triethyl orthoformate (3 mL) was added, and the mixture was stirred at 50° C. for 6 hr. Water (10 mL) was added to the mixture, and the mixture was neutralized to pH 9 with 30% aqueous ammonia solution, and extracted twice with chloroform. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=9:1) to give (E)-{2-[4-methyl-6-(1,3,4-oxadiazol-2-yl)-2-propylbenzimidazol-1-yl]methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene}acetonitrile (24 mg, 58%).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:23]=[C:22]3[C:14]([N:15]4[C:20](=[CH:21]3)[C:19](=[O:24])[NH:18][CH2:17][CH2:16]4)=[N:13][CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[CH3:25][O:26][CH2:27][CH2:28]Br.[H-].[Na+]>>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([O:10][C:11]2[CH:23]=[C:22]3[C:14]([N:15]4[C:20](=[CH:21]3)[C:19](=[O:24])[N:18]([CH2:28][CH2:27][O:26][CH3:25])[CH2:17][CH2:16]4)=[N:13][CH:12]=2)[CH2:8][CH2:9]1)([CH3:3])[CH3:2]
Reactant: COCCBr
Reactant: CC(C)N1CCC(Oc2cnc3c(c2)cc2n3CCNC2=O)CC1
Agent: [H-]
Agent: [Na+]
Product: COCCN1CCn2c(cc3cc(OC4CCN(C(C)C)CC4)cnc32)C1=O
Yield: 72 %

Procedure:
The title compound was synthesized in analogy to example 17, from 7-(1-isopropyl-piperidin-4-yloxy)-3,4-dihydro-2H-2,4a,5-triaza-fluoren-1-one (example 84), 2-bromoethyl methyl ether and sodium hydride, to give the desired product as a colorless oil (72%).