Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:8]([OH:13])[CH2:9][CH2:10][C:11]#[CH:12]>C(N(CC)CC)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:12]#[C:11][CH2:10][CH2:9][CH2:8][OH:13])[CH:3]=1
Reactant: Brc1cccnc1
Reactant: C#CCCCO
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: OCCCC#Cc1cccnc1
Temperature: 25 °C

Procedure:
3-Bromopyridine (5.4 g, 34.2 mmol) was dissolved in triethylamine (10 ml) and degassed under nitrogen. 4-Pentyn-1-ol (3.50 ml, 37.6 mmol) was added followed by bis(triphenylphosphine)palladium (II) chloride (0.245 g, 0.349 mmol) and copper(I)iodide (0.136 g, 0.714 mmol) and the resulting mixture was stirred and heated under reflux for 20 mins. when a dark brown sludge was obtained. The mixture was cooled to rt and partitioned between EtOAc (200 ml) and water (50 ml).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([C:10]#[N:11])[CH:8]=[CH:9][C:2]1=2.C([Li])CCC.[B:17](OC(C)C)([O:22]C(C)C)[O:18]C(C)C>C1COCC1>[C:10]([C:7]1[CH:8]=[CH:9][C:2]2[S:1][C:5]([B:17]([OH:22])[OH:18])=[CH:4][C:3]=2[CH:6]=1)#[N:11]
Reactant: N#Cc1ccc2sccc2c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: N#Cc1ccc2sc(B(O)O)cc2c1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a cold (−78° C.) solution of benzo[b]thiophene-5-carbonitrile (276 mg, 1.734 mmol) in anhydrous THF (5 mL) was added n-butyllithium (0.763 mL, 1.907 mmol) dropwise. The reaction mixture was stirred at −78° C. for 60 minutes. Next, a solution of triisopropyl borate (0.478 mL, 2.080 mmol) was added. The reaction mixture was stirred for 30 minutes stirring at −78° C. and then was allowed to warm to room temperature over a 2 hour period. Solvent was removed to give the title compound, which was used without purification or work up.
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:34][C:35](Br)(Br)[F:36].C([Zn]CC)C>C1COCC1>[Br:34][C:35]([F:36])=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1
Reactant: FC(Br)(Br)Br
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC[Zn]CC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(=C(F)Br)CC1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 44 %

Procedure:
To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (500 mg, 2.52 mmol), triphenylphosphine (808 mg, 3.02 mmol) and tribromofluoromethane (818 mg, 3.02 mmol) in 50 mL of anhydrous THF was added dropwise a solution of diethylzinc (1 M in hexane, 3.02 mL, 3.02 mmol) stirring at r.t. After 2.5 h, the reaction mixture was quenched with MeOH (10 mL), stirred for 30 min., evaporated to dryness in vacuo. Purification was carried out by automated flash liquid chromatography (Horizon™-Biotage) eluting with Petroleum Ether-EtOAc gradient from 95:5:0 to 90:10 to afford the title compound (326 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([O:9]C)[C:3]=1[S:11]([NH:14][CH:15]([CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)[C:16]([F:19])([F:18])[F:17])(=[O:13])=[O:12].B(Br)(Br)Br>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([OH:9])[C:3]=1[S:11]([NH:14][CH:15]([CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)[C:16]([F:18])([F:19])[F:17])(=[O:13])=[O:12]
Reactant: COc1cc(Cl)cc(Cl)c1S(=O)(=O)NC(Cc1c[nH]c2ccccc12)C(F)(F)F
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=S(=O)(NC(Cc1c[nH]c2ccccc12)C(F)(F)F)c1c(O)cc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 14.7 %

Procedure:
To a solution of 30 mg (0.06 mmol) of 2,4-dichloro-6-methoxy-N-[2,2,2-trifluoro-1-(1H-indol-3-ylmethyl)ethyl]benzenesulfonamide in 2 mL of dichloromethane was added 1 mL (1 mmol) of 1 M boron tribromide in CH2Cl2. After 1 hour, the reaction was cooled in an ice-water bath and cautiously quenched with 5-10 mL of methanol with stirring. The mixture was warmed to room temperature and the residue was dissolved in ethyl acetate and washed with three 20 mL portions of 1 M aqueous HCl, saturated aqueous sodium bicarbonate solution, and brine. The organic layers was dried over sodium sulfate, decanted, and concentrated in vacuo. The product crystallized upon concentration to afford 4 mg (13%) of the title compound.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH2:21]O)=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].S(Cl)([Cl:25])=O>ClCCl>[C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH2:21][Cl:25])=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: O=S(Cl)Cl
Reactant: CC(C)(C)c1csc(-c2cc3cc(CCCO)ccc3o2)n1
Solvent: ClCCl
Product: CC(C)(C)c1csc(-c2cc3cc(CCCCl)ccc3o2)n1
Temperature: 25 °C

Procedure:
A mixture of 3-[2-(4-tert-butylthiazol-2-yl)benzofuran-5-yl]propanol (0.40 g) and thionyl chloride (0.4 ml) in dichloromethane (5 ml) was stirred under reflux for 5 hours. After being cooled to room temperature, the solution was concentrated under reduced pressure. The resulting residue -was partitioned between aqueous sodium hydrogencarbonate solution and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give a 4-tert-butyl-2-[5-(3-chloropropyl)benzofuran-2-yl]thiazole (0.28 g).
Reaction SMILES: [CH3:1][N:2]([CH3:49])[C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[F:23])[N:15]([C:24](=[O:41])[CH2:25][NH:26][C:27]([NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([O:38]CC)=[O:37])[CH:31]=3)=[O:28])[CH:14]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[OH-].[K+]>CO.O>[C:45]([O:44][C:42]([CH:14]1[CH2:13][CH:12]([S:9]([C:6]2[CH:7]=[CH:8][C:3]([N:2]([CH3:49])[CH3:1])=[CH:4][CH:5]=2)(=[O:11])=[O:10])[CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])[N:15]1[C:24](=[O:41])[CH2:25][NH:26][C:27](=[O:28])[NH:29][C:30]1[CH:31]=[C:32]([CH:33]=[CH:34][CH:35]=1)[C:36]([OH:38])=[O:37])=[O:43])([CH3:48])([CH3:46])[CH3:47]
Reactant: CCOC(=O)c1cccc(NC(=O)NCC(=O)N2C(C(=O)OC(C)(C)C)CC(S(=O)(=O)c3ccc(N(C)C)cc3)C2c2ccccc2F)c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CN(C)c1ccc(S(=O)(=O)C2CC(C(=O)OC(C)(C)C)N(C(=O)CNC(=O)Nc3cccc(C(=O)O)c3)C2c2ccccc2F)cc1
Yield: 8.3 %

Procedure:
A The process is performed as described in Example 1A, but starting with 1.5 g of tert-butyl (2RS,4SR,5RS)-4-(4-dimethylaminophenyl)sulphonyl-1-{2-[3-(3-ethoxycarbonylphenyl)ureido]acetyl}-5-(2-fluorophenyl)-2-pyrrolidinecarboxylate and 0.12 g of potassium hydroxide in a mixture of 60 cm3 of methanol and 20 cm3 of distilled water. After treatment, 0.12 g of (2RS,4SR,5RS)-3-(3-{2-[2-tert-butoxycarbonyl-4-(4-dimethylaminophenyl)sulphonyl-5-(2-fluorophenyl)-1-pyrrolidinyl]-2-oxoethyl}ureido)benzoic acid is obtained [Rf=0.4; eluent: methylene chloride/methanol (90/10); 1H NMR spectrum (250 MHz, (CD3)2SO with addition of a few drops of CD3COOD, at a temperature of 393 K, δ in ppm): 1.52 (s, 9H: C(CH3)3); 2.43 and 2.77 (2 mts, 1H each: CH2 at 3); 3.04 (s, 6H: N(CH3)2); 3.63 and 3.99 (broad d and d respectively, J=17 Hz, 1H each: COCH2N); 3.86 (mt, 1H: H4); 4.56 (broad t, J=8 Hz, 1H: H2); 5.71 (d, J=3 Hz, 1H: H5); 6.81 (d, J=8.5 Hz, 2H: H of the aromatic at 4 (H ortho to the N(CH3)2)); from 7.00 to 7.70 (mt, 6H: aromatic H); 7.68 (d, J=8.5 Hz, 2H: H of the aromatic at 4 (H meta to the N (CH3)2)); 7.80 (mt 1H: H of the aromatic at 5 (H6)); 8.00 (mt, 1H: aromatic H (H2: ortho to the COOH))].
Reaction SMILES: C([Si]([O:8][CH:9]1[CH2:25][CH2:24][CH:13]2[CH2:14][O:15][C:16]3[C:21]([C:12]2([S:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH2:11][CH2:10]1)=[C:20]([F:22])[CH:19]=[CH:18][C:17]=3[F:23])(C)C)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CCOC(C)=O.C(Cl)Cl>C1COCC1>[Cl:35][C:32]1[CH:31]=[CH:30][C:29]([S:26]([C:12]23[CH2:11][CH2:10][CH:9]([OH:8])[CH2:25][CH2:24][CH:13]2[CH2:14][O:15][C:16]2[C:21]3=[C:20]([F:22])[CH:19]=[CH:18][C:17]=2[F:23])(=[O:28])=[O:27])=[CH:34][CH:33]=1
Reactant: CC(C)(C)[Si](C)(C)OC1CCC2COc3c(F)ccc(F)c3C2(S(=O)(=O)c2ccc(Cl)cc2)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=S(=O)(c1ccc(Cl)cc1)C12CCC(O)CCC1COc1c(F)ccc(F)c12
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of tert-butyl-[11a-(4-chloro-benzenesulfonyl)-1,4-difluoro-6,6a,7,8,9,10,11,11a-octahydro-cyclohepta[c]chromen-9-yloxy]-dimethyl-silane (700 mg, 1.30 mmol) in THF (10 mL) at 0° C. was treated with TBAF (1 M in THF, 2.6 mL, 2.6 mmol) and warmed to ambient temperature. After 12 h, the reaction mixture was quenched with saturated aqueous NH4Cl and extracted with EtOAc (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated in vacuo. Flash chromatography (2→20% EtOAc/CH2Cl2) afforded Example 344A1 (200 mg, Rf=0.49, 10% EtOAc/CH2Cl2): 1H NMR (CDCl3 400 MHz) δ 7.61 (d, J=8.7 Hz, 2H), 7.49 (d, J=8.7 Hz, 2H), 7.04 (m, 1H), 6.40 (m, 1H), 5.13 (dd, J=11.7, 2.2 Hz, 1H), 4.26 (dd, J=11.0, 2.2 Hz, 1H), 4.14 (m, 1H), 2.85 (d, J=6.6 Hz, 1H), 2.52 (ddd, J=14.6, 10.3, 2.2 Hz, 1H), 2.34 (m, 1H), 2.22 (m, 1H), 1.87-1.62 (m, 5H); followed by Example 344B1 (130 mg, Rf=0.33, 10% EtOAc/CH2Cl2): 1H NMR (CDCl3 400 MHz) δ 7.64 (d, J=8.8 Hz, 2H), 7.50 (d, J=8.8 Hz, 2H), 7.04 (m, 1H), 6.40 (m, 1H), 5.13 (dd, J=11.0, 2.2 Hz, 1H), 4.26 (dd, J=11.7, 2.2 Hz, 1H), 3.67 (m, 1H), 2.96 (m, 1H), 2.75 (m, 1H), 2.19 (m, 1H), 2.02 (m, 1H), 1.81-1.49 (m, 5H).
Reaction SMILES: C([O:3][C:4](=[O:27])[CH2:5][O:6][CH2:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([C:14]2[CH:15]=[N:16][C:17]3[N:18]([C:24](=[O:26])[NH2:25])[CH2:19][CH2:20][CH2:21][C:22]=3[CH:23]=2)[CH:13]=1)C.[Li+].[OH-].CCO>O>[C:24]([N:18]1[C:17]2[N:16]=[CH:15][C:14]([C:12]3[CH:13]=[C:8]([CH2:7][O:6][CH2:5][C:4]([OH:27])=[O:3])[CH:9]=[N:10][CH:11]=3)=[CH:23][C:22]=2[CH2:21][CH2:20][CH2:19]1)(=[O:26])[NH2:25]
Reactant: CCOC(=O)COCc1cncc(-c2cnc3c(c2)CCCN3C(N)=O)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: NC(=O)N1CCCc2cc(-c3cncc(COCC(=O)O)c3)cnc21
Yield: 86.5 %

Procedure:
[5-(8-Carbamoyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-pyridin-3-ylmethoxy]-acetic acid ethyl ester (1.0 g, 2.7 mmol) and LiOH (0.10 g, 4.2 mmol) are mixed in H2O (10 mL) and EtOH (10 mL) and stirred at room temperature overnight. The reaction mixture is concentrated under vacuum and treated with 1 N HCl, and ethyl acetate. The organic layer is concentrated to give [5-(8-carbamoyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-pyridin-3-ylmethoxy]-acetic acid (0.80 g).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:17]([C:18](=[O:24])[CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:16][NH:15][C:12]2=[CH:13][N:14]=1.Cl[C:26]1[N:27]=[N:28][C:29]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:30][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:17]([C:18](=[O:24])[CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:16][N:15]([C:26]3[N:27]=[N:28][C:29]([O:32][CH:33]([CH3:35])[CH3:34])=[CH:30][CH:31]=3)[C:12]2=[CH:13][N:14]=1
Reactant: CC(C)Oc1ccc(Cl)nn1
Reactant: CCC(CC)C(=O)c1c[nH]c2cnc(-c3c(C)cccc3C)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCC(CC)C(=O)c1cn(-c2ccc(OC(C)C)nn2)c2cnc(-c3c(C)cccc3C)cc12
Temperature: 149 °C

Procedure:
To a solution of 1-[5-(2,6-dimethyl-phenyl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-ethyl-butan-1-one (100 mg, 0.31 mmol) (Step 4, Example 1) in 2 mL of DMF, 3-chloro-6-isopropoxy-pyridazine (161 mg, 0.93 mmol) is added, followed by Cs2CO3 (306 mg, 0.93 mmol). The mixture is heated to 149° C. for 18 h under nitrogen. The mixture is diluted with EtOAc (7 mL) and washed with water (3×5 mL) and brine (5 mL), dried (Na2SO4), and concentrated under reduced pressure. Chromatography of the residue on silica gel (hexane-EtOAc, 1:1) gives 1-[5-(2,6-dimethyl-phenyl)-1-(6-isopropoxy-pyridazin-3-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-ethyl-butan-1-one as colorless oil.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]2[C:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[C:18]([OH:25])[CH:19]=[CH:20][CH:21]=4)[N:16]=3)=[CH:13][N:14]=[C:8]2[CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:32][C:33]1([CH2:46]OS(C)(=O)=O)[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1>CC(N(C)C)=O>[F:32][C:33]1([CH2:46][O:25][C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:17]=2[N:16]=[C:15]([C:12]2[N:9]4[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:7][C:8]4=[N:14][CH:13]=2)[CH:24]=[CH:23]3)[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:37][CH2:38]1
Reactant: COCCOc1ccn2c(-c3ccc4cccc(O)c4n3)cnc2c1
Reactant: CC(C)(C)OC(=O)N1CCC(F)(COS(C)(=O)=O)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: COCCOc1ccn2c(-c3ccc4cccc(OCC5(F)CCN(C(=O)OC(C)(C)C)CC5)c4n3)cnc2c1
Temperature: 90 °C
Yield: 13.4 %

Procedure:
2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.050 g, 0.149 mmol) was dissolved in DMA (0.5 mL) and treated with Cs2CO3 (0.097 g, 0.29 mmol). After stirring for several minutes, tert-butyl 4-fluoro-4-((methylsulfonyloxy)methyl)piperidine-1-carboxylate (0.053 g, 0.171 mmol) was added. The mixture was heated to 90° C. for 40 hours. The entire reaction mixture was applied to a SiO2 column and eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (11 mg). MS ESI (+) m/z 551.1 (M+1) detected.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[CH:12][CH:13]=[C:8]3[CH:7]=[C:6]2[CH:14]=O)[CH2:3][CH2:2]1.[C:16]([O:20][C:21](=[O:42])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:41])[C:30]2[CH:35]=[CH:34][C:33]([NH:36][CH3:37])=[C:32]([N+:38]([O-])=O)[CH:31]=2)[CH2:24]1)([CH3:19])([CH3:18])[CH3:17].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O.C(Cl)Cl>[C:16]([O:20][C:21](=[O:42])[NH:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([C:29]([C:30]2[CH:35]=[CH:34][C:33]3[N:36]([CH3:37])[C:14]([C:6]4[N:5]([CH2:4][CH:1]5[CH2:2][CH2:3]5)[C:9]5=[N:10][CH:11]=[CH:12][CH:13]=[C:8]5[CH:7]=4)=[N:38][C:32]=3[CH:31]=2)=[O:41])[CH2:24]1)([CH3:19])([CH3:17])[CH3:18]
Reactant: O=Cc1cc2cccnc2n1CC1CC1
Reactant: CNc1ccc(C(=O)N2CCC[C@@H](NC(=O)OC(C)(C)C)C2)cc1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Solvent: O
Product: Cn1c(-c2cc3cccnc3n2CC2CC2)nc2cc(C(=O)N3CCC[C@@H](NC(=O)OC(C)(C)C)C3)ccc21
Temperature: 25 °C
Yield: 39.3 %

Procedure:
A solution of 1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2 g, 8.99 mmol) in ethanol (90 mL) was added to a round bottom flask containing (R)-tert-butyl(1-(4-(methylamino)-3-nitrobenzoyl)piperidin-3-yl)carbamate (3.4 g, 8.98 mmol) and the resulting solution stirred at room temperature. A solution of sodium dithionite (3.14 g, 15.33 mmol) in water (45 mL) was added portionwise to the reaction mixture. The reaction mixture was heated to 100° C. and stirred under nitrogen for 4 hours. The reaction mixture was concentrated under vacuum then diluted with DCM (150 ml) and water (150 ml). The organic layer was collected and the aqueous layer washed with DCM (3×100 ml). Organic layers were collected and backwashed with water (2×100 ml). The organic layer was collected, dried with Na2SO4, filtered through a hydrophobic frit and concentrated under vacuum to yield a crude product. This was dissolved in a minimum volume of DCM and purified using Biotage SP4 on a 100 g SNAP silica cartridge. The column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV. Appropriate fractions were collected and concentrated under vacuum. This was dried under vacuum to yield the title compound as a yellow solid (1.867 g).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([Br:9])[CH:6]=[C:5]([Br:10])[C:3]=1[NH2:4].S(=O)(=O)(O)O.N([O-])=O.[Na+].NC(N)=O.[N-:24]=[N+:25]=[N-].[Na+]>O.C(O)(=O)C>[N:4]([C:3]1[C:2]([Br:1])=[CH:8][C:7]([Br:9])=[CH:6][C:5]=1[Br:10])=[N+:24]=[N-:25]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1c(Br)cc(Br)cc1Br
Agent: NC(N)=O
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: [N-]=[N+]=Nc1c(Br)cc(Br)cc1Br
Temperature: 10 °C
Yield: 92.8 %

Procedure:
2,4,6-Tribromoaniline (34.16 g, 103.6 mmol) was mixed with acetic acid (600 mL) and sulfuric acid (130 mL) at room temperature. The mixture was stirred to obtain a solution and then cooled in an ice bath to an internal temperature of 10° C. A solution of NaNO2 (7.65 g, 111 mmol) in water (22 mL) was added dropwise over 30 minutes while maintaining the internal temperature of the reaction mixture below 12° C. The reaction mixture was allowed to stir for 30 minutes at the same temperature. A solution of urea (0.90 g) in water (2 mL) was added and the mixture stirred for an additional 10 minutes. A solution of NaN3 (7.65 g, 118 mmol) in water (22 mL) was slowly added and the mixture stirred for an additional 1 hour. Cold water (900 mL) was then slowly added in portions and the mixture stirred for 30 minutes. The precipitate was filtered, washed with water, dissolved in diethyl ether, dried over sodium sulfate and concentrated to give the subtitle compound as an off-white solid (34.2 g, 93%).
Reaction SMILES: C([O:3][C:4]([C:6]1([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Br:17])[CH:12]=2)[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5])C.[OH-].[Li+].C1COCC1.CO>O>[Br:17][C:13]1[CH:12]=[C:11]([C:6]2([C:4]([OH:5])=[O:3])[CH2:10][CH2:9][CH2:8][CH2:7]2)[CH:16]=[CH:15][CH:14]=1
Reactant: CCOC(=O)C1(c2cccc(Br)c2)CCCC1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)C1(c2cccc(Br)c2)CCCC1
Reaction time: 18 h
Yield: 80.7 %

Procedure:
A mixture of 1-(3-bromo-phenyl)-cyclopentanecarboxylic acid ethyl ester [3.42 g, 11.51 mmol], lithium hydroxide (579 mg, 13.81 mmol), THF (13 mL), MeOH (13 mL) and water (13 mL) is vigorously stirred for 18 hours. The mixture is concentrated and the residue is diluted with water (50 mL). The aqueous mixture is acidified with concentrated HCl to pH 1 and extracted twice with EtOAc (50 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 1-(3-bromo-phenyl)-cyclopentanecarboxylic acid [2.5 g, 80.6%] as a solid, which is used without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[CH2:5][N:6]([C:14](=[O:28])[C@@H:15]([NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:16]([CH3:18])[CH3:17])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].[N+:30](C1C=C(C=CC=1)C=O)([O-:32])=[O:31].C(OC(=O)CNCC1C=CC=CC=1)C>>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][N:6]([C:14](=[O:28])[C@@H:15]([NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:16]([CH3:18])[CH3:17])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([N+:30]([O-:32])=[O:31])[CH:9]=1)[CH3:2]
Reactant: CCOC(=O)CN(Cc1ccccc1)C(=O)[C@@H](NC(=O)c1ccccc1)C(C)C
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Agent: CCOC(=O)CNCc1ccccc1
Product: CCOC(=O)CN(Cc1cccc([N+](=O)[O-])c1)C(=O)[C@@H](NC(=O)c1ccccc1)C(C)C

Procedure:
Compound 734 was prepared by a method similar to the method used to prepare compound 703 except benzaldehdye was replaced with 3-nitrobenzaldehyde in the preparation of 701. ##STR113##
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:19]([NH2:22])(=[O:21])=[O:20])[CH:5]=[C:6]([N+:16]([O-:18])=[O:17])[C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C([Sn](CCCC)(CCCC)[C:28]1[N:33]=[CH:32][CH:31]=[CH:30][N:29]=1)CCC.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>C(#N)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:10]1([CH2:9][NH:8][C:7]2[C:2]([C:28]3[N:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:3][C:4]([S:19]([NH2:22])(=[O:21])=[O:20])=[CH:5][C:6]=2[N+:16]([O-:18])=[O:17])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncccn1
Reactant: NS(=O)(=O)c1cc(Br)c(NCC2CCCCC2)c([N+](=O)[O-])c1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1coc(P(c2ccco2)c2ccco2)c1
Solvent: CC#N
Product: NS(=O)(=O)c1cc(-c2ncccn2)c(NCC2CCCCC2)c([N+](=O)[O-])c1

Procedure:
A solution of Example 26A (270 mg, 0.69 mmol), 2-(tributylstannyl)pyrimidine (305 uL, 0.83 mmol), Pd2(dba)3 (32 mg, 0.034 mmol), and tris-(2-furyl)phosphine (32 mg, 0.10 mmol) in acetonitrile (2 mL) was heated to reflux for 48 hours and concentrated. The concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes to provide the desired product. MS (ESI(+)) m/e 392 (M+H)+.
Reaction SMILES: [CH2:1]([C:5]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]([O:30]C(C)(C)C)=[O:29])=[CH:18][CH:17]=2)[C:13](=[O:35])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:36]([CH3:38])[CH3:37])[CH:11]=2)[N:6]=1)[CH2:2][CH2:3][CH3:4].FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>C(Cl)Cl>[CH2:1]([C:5]1[N:14]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:28]([OH:30])=[O:29])=[CH:18][CH:17]=2)[C:13](=[O:35])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:36]([CH3:37])[CH3:38])[CH:11]=2)[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2ccc(C(C)C)cc2c(=O)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCCCc1nc2ccc(C(C)C)cc2c(=O)n1Cc1ccc(-c2ccccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of 2-n-butyl-3-[(2'-(t-butoxycarbonyl)biphen-4-yl)-methyl]-6-isopropylquinazolin-4(3H)-one (0.198 g, 0.44 mmol) from Example 36B in a mixture of methylene chloride (3 ml) and anhydrous trifluoro acetic acid (3 ml) containing anisole (0.05 ml) was stirred at room temperature for 4 hours. The solvent was then removed under reduced pressure and the residue was triturated with dry ether to give the solid product, which was then collected by filteration and dried in vacuo over NaOH and P2O5 to give the desired product as the mono trifluoroacetate salt. 1H-NMR(CDCl3): 0.91 (t, 3H, J=7.35 Hz), 1.32 (d, 6H, J=6.9 Hz), 1.47 (m, 2H), 1.72 (m, 2H), 3.12 (m, 3H), 5.48 (s, 2H), 7.14-7.96 (m, 11H), 8.16 (d, 1H, J=1.9 Hz). FAB-MS: m/e 399 (M+H).