Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:17]([OH:18])[C@@H:16]([OH:19])[C@@H:15]([CH3:20])[O:14][C@H:10]1[S:11][CH2:12][CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:28]([O:18][C@H:17]1[C@@H:16]([OH:19])[C@@H:15]([CH3:20])[O:14][C@@H:10]([S:11][CH2:12][CH3:13])[C@@H:9]1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CCS[C@@H]1O[C@H](C)[C@H](O)[C@H](O)[C@H]1OCc1ccccc1
Reactant: O=C(Cl)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCS[C@@H]1O[C@H](C)[C@H](O)[C@H](OC(=O)c2ccccc2)[C@H]1OCc1ccccc1
Temperature: -30 °C
Reaction time: 3 h
Yield: 80.7 %

Procedure:
To a solution of ethyl 2-O-benzyl-6-deoxy-1-thio-β-D-galactopyranoside (1.03 g, 3.45 mmol) and DMAP (126 mg, 1.0 mmol) in 10 mL of dry CH2Cl2 at −30° C. was added Et3N (1.92 mL, 13.8 mmol). Benzoyl chloride (0.4 mL, 3.45 mmol) was added to this mixture in a dropwise fashion, and the stirred at −30° C. for 3 hr. The reaction was then quenched by the addition of MeOH (2 mL) and the mixture was gradually warmed to room temperature after which the resulting mixture was diluted with EtOAc (250 mL). The solution was washed with saturated NaHCO3 solution (2×20 mL), water (30 mL), dried over Na2SO4, concentrated and purified by flash chromatography (3:1 to 1:1 hexane/EtOAc) to give 1.12 g (80%) of the title product. [α]D=96.9° (c=1, CHCl3); 1H NMR (CDCl3) 8.09-8.03 (m, 2H), 7.56 (t, 1H, J=7.4 Hz), 7.49 (m, 2H), 7.22 (m, 2H), 7.18 (m, 3H), 5.28 (dd, 1H, J=3.0, 9.6 Hz), 4.87 (d, 1H, J=10.6 Hz), 4.67 (d, 1H, J=10.6 Hz), 4.56 (d, 1H, J=9.7 Hz), 4.12 (m, 1H), 3.85 (t, 1H, J=9.8 Hz), 3.80 (m, 1H), 2.81 (m, 2H), 1.93 (d, 1H, J=6.7 Hz), 1.36 (m, 6H); 13C NMR (CDCl3) 166.2, 138.0, 133.7, 130.2, 130.1, 128.9, 128.7, 128.6, 128.2, 85.7, 78.1, 77.6, 76.5, 76.0, 74.7, 70.9, 25.6, 16.9, 15.4; MS: calcd for C22H26O5SNa 425.1. found m/z 425.2 (M+Na).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[N:27]=3)[CH2:18]2)[N:3]=1.[NH2:34][NH2:35]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[C:14]3[C:11]([C:12]([NH2:13])=[N:34][NH:35]3)=[CH:10][CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:27]=3)[CH2:18]2)[N:3]=1
Reactant: N#Cc1ccc(-c2cc(N3CCOC(c4nc(-c5ccccc5)c[nH]4)C3)nc(N)n2)cc1F
Reactant: NN
Solvent: CCO
Product: Nc1nc(-c2ccc3c(N)n[nH]c3c2)cc(N2CCOC(c3nc(-c4ccccc4)c[nH]3)C2)n1
Reaction time: 1 h
Yield: 69.1 %

Procedure:
A mixture of 4-{2-amino-6-[2-(4-phenyl-1H-imidazol-2-yl)-4-morpholinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (310 mg, 0.702 mmol) and hydrazine (2.5 mL, 79 mmol) in ethanol (4 mL) was heated under microwave conditions with stirring for 1 hour. The mixture was concentrated to afford the crude title compound (400 mg) as a yellow solid. This material was combined with another batch of crude title compound (100 mg). The combined material was washed with CH2Cl2 (2×8 mL) and dried in vacuo. The resulting residue was purified by Prep-HPLC using CH3CN in water (0.5% ammonium hydrogen carbonate in water) from 25% to 30% to afford the title compound (220 mg) as a yellow solid. LC-MS (ES) m/z=454 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.08-3.14 (m, 1H), 3.18-3.24 (m, 1H), 3.72 (m, 1H), 4.04-4.07 (m, 1H), 4.30-4.34 (m, 1H), 4.59-4.64 (m, 1H), 4.73-4.75 (m, 1H), 5.39 (s, 2H), 6.21 (s, 2H), 6.71 (s, 1H), 7.16-7.20 (m, 1H), 7.31-7.36 (m, 2H), 7.61-7.63 (m, 2H), 7.71 (d, J=8.4 Hz, 1H), 7.78 (d, J=7.2 Hz, 2H), 7.99 (s, 1H), 11.53 (s, 1H), 12.33-12.62 (m, 1H).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[OH:4].O=[C:13]([CH3:27])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][C:23]([O:25][CH3:26])=[O:24].C1C=CC=CC=1.C([BH3-])#N.[Na+]>CO>[CH3:26][O:25][C:23]([CH2:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[O:15][CH2:14][CH:13]([NH:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[OH:4])[CH3:27])=[O:24]
Reactant: NCC(O)c1cccc(Cl)c1
Reactant: COC(=O)Cc1ccccc1OCC(C)=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)Cc1ccccc1OCC(C)NCC(O)c1cccc(Cl)c1
Yield: 70.4 %

Procedure:
Following a procedure similar to that described in Example 6, but using 2 g of 2-amino-1-(3-chlorophenyl)ethanol (prepared as described in Preparation 8), 3.11 g of methyl 2-(2-oxopropoxy)phenylacetate (prepared as described in Preparation 18), 70 ml of benzene, 60 ml of absolute methanol and 2.5 g of sodium cyanoborohydride, 3.1 g of the title compound were obtained having an Rf=0.30 (thin layer chromatography over silica gel, using ethyl acetate as the developing solvent).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH2:23][NH2:24])[CH:7]=1)[CH3:2].N1C=CC=CC=1.[Cl:32][C:33]1[CH:41]=[CH:40][C:36]([C:37](Cl)=[O:38])=[CH:35][CH:34]=1>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:20])([F:21])[F:22])=[CH:15][C:14]=2[CH2:23][NH:24][C:37](=[O:38])[C:36]2[CH:40]=[CH:41][C:33]([Cl:32])=[CH:34][CH:35]=2)[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1cccc(Oc2ccc(C(F)(F)F)cc2CN)c1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCOC(=O)Cc1cccc(Oc2ccc(C(F)(F)F)cc2CNC(=O)c2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To [3-(2-aminomethyl-4-trifluoromethyl-phenoxy)-phenyl]-acetic acid ethyl ester (0.084 g, 0.24 mmol) and pyridine (2.0 mL) in CH2Cl2 (2.5 mL) was added 4-chlorobenzoyl chloride (0.04 mL, 0.29 mmol), and the reaction was stirred for 30 minutes at room temperature. The mixture was partitioned between CH2Cl2 and 1N aqueous HCl, and the organic layer was separated and washed twice with 1N aqueous HCl. The organic layer was dried and concentrated, resulting in the formation of a white precipitate. The precipitate was filtered off, and the filtrate was concentrated to give the title compound.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[N:9][CH:10]=1)=O.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][N:18]=1>C(#N)C>[I:23][C:20]1[CH:21]=[CH:22][C:17]2[N:18]([CH:2]=[C:3]([C:5]3[CH:6]=[CH:7][C:8]([N:11]4[N:15]=[CH:14][CH:13]=[N:12]4)=[N:9][CH:10]=3)[N:16]=2)[CH:19]=1
Reactant: Nc1ccc(I)cn1
Reactant: O=C(CBr)c1ccc(-n2nccn2)nc1
Solvent: CC#N
Product: Ic1ccc2nc(-c3ccc(-n4nccn4)nc3)cn2c1
Temperature: 100 °C
Yield: 35.3 %

Procedure:
20.4 mg (corresponding to 0.0764 mmol) of 5-(2-bromoacetyl)-2-(2H-1,2,3-triazole-2-yl)pyridine and 16.8 mg (corresponding to 0.0764 mmol) of 2-amino-5-iodopyridine were dissolved in 2.0 mL of acetonitrile. The resulting solution was heated under reflux for 1.5 hours in an oil bath at 100° C. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 2 mL of water and 2 mL of methanol. Then, about 1 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 10 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 10.4 mg (corresponding to 0.027 mmol) of 6-iodo-2-[2-(2H-1,2,3-triazole-2-yl)pyridine-5-yl]imidazo[1,2-a]pyridine (FIG. 2, step 3).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21](Cl)[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]3[Cl:33])([C:10]2[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.Cl.[CH3:35][NH:36][O:37][CH3:38].CN(C)C=O>CCOC(C)=O>[Cl:33][C:19]1[C:18]2[C:23](=[CH:24][CH:25]=[C:16]([C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)([C:10]3[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=3)[OH:9])[CH:17]=2)[N:22]=[C:21]([N:36]([O:37][CH3:38])[CH3:35])[C:20]=1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CNOC
Reactant: Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2nc(Cl)c(-c3ccccc3)c(Cl)c2c1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CON(C)c1nc2ccc(C(O)(c3ccc(Cl)cc3)c3cncn3C)cc2c(Cl)c1-c1ccccc1
Temperature: 100 °C

Procedure:
(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (250 mg, 0.505 mmol, Example 65), N,O-dimethylhydroxylamine hydrochloride (1.01 g, 10.1 mmol), and dimethylformamide (2 mL) were combined in a reaction tube, which was then sealed and heated to 100° C. for 48 hours. The contents were then cooled, transferred to a reparatory funnel, diluted with EtOAc and extracted with saturated, aqueous NH4Cl solution, followed by deionized water (4×). The organic phase was separated and dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C28H24Cl2N4O2, 518.1; m/z found, 519.2 [M+H]+; 1H NMR (400 MHz, CD3OD) δ ppm 8.14 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.70 (dd, J=8.8, 2.1 Hz, 1H), 7.67 (s, 1H), 7.47 (dd, J=11.4, 4.3 Hz, 2H), 7.39 (dt, J=4.4, 1.8 Hz, 1H), 7.36 (d, J=4.1 Hz, 4H), 7.26 (dd, J=8.2, 1.3 Hz, 2H), 6.28 (s, 1H), 3.46 (s, 3H), 3.05 (s, 3H), 2.76 (s, 3H).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].I[C:14]1[C:22]2[C:17](=[N:18][CH:19]=[N:20][C:21]=2[NH2:23])[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.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>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([CH:24]([CH3:26])[CH3:25])[N:15]=[C:14]([C:6]3[CH:5]=[C:4]([C:1](=[O:3])[CH3:2])[CH:9]=[CH:8][CH:7]=3)[C:22]=12
Reactant: CC(=O)c1cccc(B(O)O)c1
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
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: [Na+]
Solvent: COCCOC
Solvent: CCO
Product: CC(=O)c1cccc(-c2nn(C(C)C)c3ncnc(N)c23)c1
Temperature: 80 °C
Yield: 18.2 %

Procedure:
A solution of 3-Acetylphenylboronic acid (23 mg, 0.14 mmol) in EtOH (3.3 mL) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (40 mg, 0.13 mmol) in DME (12 mL). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 mL) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA55 (7 mg, 18% yield). ESI-MS (M+H)+ m/z calcd 296.1, found 296.1.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][C@H:13]2[CH2:17][N:16]([C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[CH2:26])[C@H:15]([C:36]([O:38]CC)=[O:37])[CH2:14]2)=[CH:4][C:3]=1[O:41][CH3:42]>C1COCC1.CCO.[Li+].[OH-].OS([O-])(=O)=O.[K+]>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]=[C:9]2[O:12][C@H:13]2[CH2:17][N:16]([C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:25]=[CH2:26])[C@H:15]([C:36]([OH:38])=[O:37])[CH2:14]2)=[CH:4][C:3]=1[O:41][CH3:42]
Reactant: C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)OCC
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li+]
Solvent: CCO
Solvent: C1CCOC1
Product: C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc2nccc3cc(OC)c(Br)cc23)C[C@H]1C(=O)O
Yield: 96.1 %

Procedure:
A solution of the product from Step 1 (400 mg, 0.617 mmol) in THF (5 mL), EtOH (1 mL) and 1N aqueous LiOH (4.32 mL) was stirred at RT for 2 hours. The reaction solution was diluted with 10% KHSO4 (20 mL) and extracted with ether (3×70 mL). The combined ether layers were washed with water (50 mL), brine (30 mL), dried over Na2SO4, filtered and concentrated to give the title product (368 mg). LRMS (ESI) m/z 620.4 [(M+H)+; calcd for C29H39BrN3O7: 620.2].
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][S:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[S:21]([CH3:24])(=[O:23])=[O:22])(=[O:14])=[O:13])[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[CH:32]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[CH:34][C:33]=1B(O)O.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:24][S:21]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[S:12]([NH:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[NH:4][N:3]=[C:2]2[C:34]1[CH:33]=[CH:32][C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=1)(=[O:13])=[O:14])(=[O:22])=[O:23]
Reactant: CC(C)(C)OC(=O)n1nc(I)c2cc(NS(=O)(=O)c3ccccc3S(C)(=O)=O)ccc21
Reactant: OB(O)c1ccc2ccccc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccccc1S(=O)(=O)Nc1ccc2[nH]nc(-c3ccc4ccccc4c3)c2c1
Yield: 29 %

Procedure:
2-Methylsulfonyl-N-(3-naphthalen-2-yl-1H-indazol-5-yl)benzenesulfonamide can be obtained as described in Example 59 from 0.5 g of tert-butyl 3-iodo-5-(2-methylsulfonylbenzenesulfonylamino)indazole-1-carboxylate, 298 mg of 2-naphthaleneboronic acid, 20 ml of dimethylformamide, 1.88 ml of a saturated aqueous sodium hydrogencarbonate solution and 24.5 mg of tetrakis(triphenylphosphine)palladium[0]. 120 mg of 2-methylsulfonyl-N-(3-naphthalen-2-yl-1H-indazol-5-yl)benzenesulfonamide are thus obtained in the form of a white solid melting at 221° C. (analysis C24H19N3O4S2 % calculated C, 60.36; H, 4.01; N, 8.80; O, 13.40; S, 13.43. % found C, 60.09; H, 4.06; N, 8.55; S, 13.51).
Reaction SMILES: [F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4]([OH:6])=[O:5].CCN(C(C)C)C(C)C.[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CC#N>[F:1][C:2]([F:10])([F:9])[C:3]([OH:8])([CH3:7])[C:4]([O:6][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:5]
Reactant: CC(O)(C(=O)O)C(F)(F)F
Reactant: BrCc1ccccc1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(O)(C(=O)OCc1ccccc1)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
3,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid (0.6 g, 3.80 mmol) was dissolved in MeCN (5 ml). DIPEA (0.663 ml, 3.80 mmol) was added and stirred for 5 min. Benzyl bromide (541 mg, 3.16 mmol) was added and the reaction mixture was stirred at RT for 16 h followed by 70° C. for 16 h. After cooling to RT, the solvent was removed in vacuo and the resulting residue was dissolved in DCM. The mixture was washed with water and the organic portion was separated by means of a phase separator. The solvent was removed in vacuo to afford the title compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:37])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]2[C:7]=1[C:8]([CH3:36])=[C:9]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=1)[C:10](OS(C(F)(F)F)(=O)=O)=[N:11]2.[Cl-].[Li+].[CH3:40][N:41](C)C=O>O.[C-]#N.[Zn+2].[C-]#N.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>[CH3:1][O:2][C:3](=[O:37])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]2[C:7]=1[C:8]([CH3:36])=[C:9]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:33])=[O:34])=[CH:28][CH:27]=1)[C:10]([C:40]#[N:41])=[N:11]2
Reactant: COC(=O)COc1ccc(Cl)c2nc(OS(=O)(=O)C(F)(F)F)c(Cc3ccc(S(C)(=O)=O)cc3)c(C)c12
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Cl-]
Solvent: O
Product: COC(=O)COc1ccc(Cl)c2nc(C#N)c(Cc3ccc(S(C)(=O)=O)cc3)c(C)c12
Temperature: 120 °C

Procedure:
A mixture of [8-chloro-3-(4-methanesulfonylbenzyl)-4-methyl-2-trifluoromethanesulfonyloxyquinolin-5-yloxy]acetic acid methyl ester, (0.080 g), zinc cyanide (0.010 g), tetrakis(triphenylphosphine)palladium(0) (0.030 g), and lithium chloride (0.001 g) in N,N-dimethylformamide (8.0 mL) was heated by microwave irradiation at 120° C. for 15 minutes. The mixture was diluted with water and the resulting precipitate collected by filtration, washed with water and diethyl ether and then dried to afford title compound, 0.056 g.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([O:8][CH3:9])[CH:7]=1.[CH3:11][Si:12]([C:15]#[CH:16])([CH3:14])[CH3:13].C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:10][C:5]1[CH:4]=[CH:3][C:2]([C:16]#[C:15][Si:12]([CH3:14])([CH3:13])[CH3:11])=[CH:7][C:6]=1[O:8][CH3:9]
Reactant: COc1cc(Br)ccc1Cl
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc(C#C[Si](C)(C)C)ccc1Cl
Temperature: 95 °C

Procedure:
Commercially available 5-bromo-2-chloroanisole (1.0 g, 4.52 mmol), trimethylsilylacetylene (1.07 mL, 7.5 mmol) and triethylamine (15 mL) were added to anhydrous toluene (15 mL) and degassed by purging with nitrogen. Bis(acetato)bis(triphenylphosphine)palladium II (340 mg, 0.45 mmol) was added and the reaction mixture was heated to ˜95° C. for 30 min. The reaction mixture was cooled to room temperature, filtered to remove the catalyst, and diluted with ethyl acetate (150 mL). The organic layer was washed with saturated sodium bicarbonate (50 mL) and brine (50 mL) separated, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography over silica gel eluted with hexane/ethyl acetate 20:1 to yield A60.1 (807 mg, 75%). 1H NMR (400 MHz): δ 7.40-7.25 (m, 2H), 7.10-7.00 (m, 1H), 3.90, (s, 3H), 0.24 (s, 9H).
Reaction SMILES: Br[C:2]1[C:10]2[CH2:9][CH2:8][N:7]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][C:18]4=[O:23])=[CH:13][CH:12]=3)[C:6](=[O:24])[C:5]=2[N:4]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[N:3]=1.CNC.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C1(C)C=CC=CC=1.O1CCOCC1>[CH3:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([N:4]2[C:5]3[C:6](=[O:24])[N:7]([C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][CH2:20][CH2:19][C:18]5=[O:23])=[CH:13][CH:12]=4)[CH2:8][CH2:9][C:10]=3[CH:2]=[N:3]2)=[CH:30][CH:29]=1
Reactant: COc1ccc(-n2nc(Br)c3c2C(=O)N(c2ccc(N4CCCCC4=O)cc2)CC3)cc1
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: CNC
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: COc1ccc(-n2ncc3c2C(=O)N(c2ccc(N4CCCCC4=O)cc2)CC3)cc1
Temperature: 85 °C
Yield: 20 %

Procedure:
To 3-bromo-1-(4-methoxyphenyl)-6-[4-(2-oxo-1-piperidinyl)phenyl]-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one (Example 21) (0.15 g, 0.3 mmol), dimethylamine (2M THF, 1.5 mL, 3 mmol), sodium t-butoxide (88 mg, 0.9 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (7 mg), was added toluene/dioxane (1:1) (15 mL) and the mixture was degassed with N2. Pd2(dba)3 was added and the reaction was heated to 85° C. for 24 h. The reaction was cooled, diluted with ethyl acetate and filtered through Celite®. Purification by HPLC and freeze-drying afforded 25 mg (18%) of the title compound; HRMS (M+Na)+ for C24H24NaN4O3 was 439.1726; 1H NMR (CDCl3) δ 7.59 (s, 1H), 7.47 (d, j=8.8 Hz, 2H), 7.36 (d, j=8.8 Hz, 2H), 7.26 (d, j=9.1 Hz, 2H), 6.92 (d, j=9.2 Hz, 2H), 4.10 (t, j=6.6 Hz, 2H), 3.60 (m, 2H), 3.81 (s, 3H), 3.03 (t, j=6.6 Hz, 2H), 2.57 (m, 2H), 1.94 (m, 4H) ppm.
Reaction SMILES: [CH2:1]([Zn]CC)C.FC(F)(F)C(O)=O.C(I)I.[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C:22](=[CH2:26])[CH2:21][CH2:20]2>>[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C:22]1([CH2:1][CH2:26]1)[CH2:21][CH2:20]2
Reactant: C=C1CCc2cc(Br)ccc21
Reactant: CC[Zn]CC
Solvent: ICI
Solvent: O=C(O)C(F)(F)F
Product: Brc1ccc2c(c1)CCC21CC1
Yield: 94.9 %

Procedure:
The title compound was synthesized in analogy to example S87 using diethyl zinc (3.25 ml, 1M solution in hexane, 3.25 mmol), trifluoroacetic acid (251 μl, 3.25 mmol), CH2I2 (262 μl, 3.25 mmol) and 5-bromo-1-methyleneindan (340 mg, 1.63 mmol). The isolated residue was purified by flash column chromatography (100% pentane) to give 5′-bromo-2′,3′dihydro-spiro[cyclopropane1,1′-[1H]indene](345 mg, 95%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 7.40-7.29 (m, 3H), 3.02 (apt t, J=7.5 Hz, 2H), 2.11 (apt t, J=7.5 Hz, 2H), 0.96-0.84 (m, 4H).
Reaction SMILES: [Si:1]([O:18][C@H:19]1[CH2:24][C@@H:23]([C:25]([NH:27][C@:28]2([C:33]([O:35][CH3:36])=[O:34])[CH2:30][C@H:29]2C=C)=[O:26])[C@H:22]([C:37](=[O:46])[N:38]([CH2:40][CH2:41][CH2:42][CH2:43][CH:44]=[CH2:45])[CH3:39])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>ClC(Cl)C>[Si:1]([O:18][C@@H:19]1[CH2:20][CH2:21][C@H:22]2[C:37](=[O:46])[N:38]([CH3:39])[CH2:40][CH2:41][CH2:42][CH2:43][CH:44]=[CH:45][C@@H:30]3[CH2:29][C@@:28]3([C:33]([O:35][CH3:36])=[O:34])[NH:27][C:25](=[O:26])[C@@H:23]2[CH2:24]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=CCCCCN(C)C(=O)[C@@H]1CC[C@@H](O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C[C@H]1C(=O)N[C@]1(C(=O)OC)C[C@H]1C=C
Agent: COC(=O)[C@@]12C[C@H]1/C=C\CCCCN(C)C(=O)[C@@H]1CC[C@@H](O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)C[C@H]1C(=O)N2
Solvent: CC(Cl)Cl
Product: COC(=O)[C@@]12C[C@H]1C=CCCCCN(C)C(=O)[C@@H]1CC[C@@H](O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)C[C@H]1C(=O)N2
Temperature: 25 °C

Procedure:
To a solution of compound 41 (0.74 mmol) in dichloroethane (700 mL), degassed for 45 min by bubbling nitrogen, was Zhan 1B (4%, 22 mg) at 80° C. under continuous degassing with nitrogen. After the reaction was refluxed for 1 hr, a second portion of Zhan 1B (22 mg) was added. After heating for 1.5 hr, the reaction mixture was cooled down to room temperature, poured onto a silica pad, and eluted with DCM. The crude material was purified by chromatography on silica gel (DCM/MeOH) to yield compound 42 as a brown solid in 81% yield. MS (ESI, EI+): m/z=617 (MH+).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)C)=O)=O)(C)C.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=1.[N:42]([CH2:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52]O)=[CH:48][CH:47]=1)=[N+:43]=[N-:44]>C1COCC1>[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][CH2:52][C:49]2[CH:48]=[CH:47][C:46]([CH2:45][N:42]=[N+:43]=[N-:44])=[CH:51][CH:50]=2)=[CH:37][CH:36]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: [N-]=[N+]=NCc1ccc(CO)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: [N-]=[N+]=NCc1ccc(COc2ccc(Cl)cc2)cc1
Temperature: -40 °C
Reaction time: 0.17 h

Procedure:
Triphenylphosphine (4.33 g, 16.5 mmol) was dissolved in dry THF (20 mL) under an atmosphere of argon. After cooling to −40° C., diisopropyl-azodicarboxylate (DIAD, 3.2 mL, 16.5 mmol) was added and the mixture was stirred at −40° C. for 10 min. A solution of 4-chlorophenol (2.12 g, 16.5 mmol) and (4-azidomethyl-phenyl)-methanol (2.45 g, 15 mmol) in dry THF (10 mL) was added dropwise. After addition, the cooling bath was removed and stirring was continued for 1 h. The solution was diluted with Et2O (150 mL) and washed with pH-7-phosphate buffer solution (1×50 mL). The organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure. The resulting residue was purified by flash chromatography (2-3% EtOAc in hexane) to give the title compound.