Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N12CCN(CC1)CC2.[C:9]1([SH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:16]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)(=[O:19])[C:17]#[CH:18].[OH-].[Na+]>C1COCC1>[C:9]1([S:15][CH:18]=[CH:17][C:16]([O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)=[O:19])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Sc1ccccc1
Reactant: C#CC(=O)Oc1ccc(-c2ccccc2)cc1
Agent: C1CN2CCN1CC2
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(C=CSc1ccccc1)Oc1ccc(-c2ccccc2)cc1
Reaction time: 0.33 h
Yield: 85.9 %

Procedure:
To a stirred solution of 1,4-diazabicyclo[2.2.2]octane (DABCO, 10 mg, 0.89 mmol) and thiophenol (99 mg, 0.89 mmol) in dry THF (20 mL) at RT was added compound 1 (200 mg, 0.89) dissolved in dry THF (2 mL) through a syringe over 12 min. The reaction mixture was further stirred for 20 min. 10% NaOH(aq) was added. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and the solvent was removed by evaporation. The crude product was purified by column chromatography using ethyl acetate:hexane (2:8) as an eluent to give compound 4 (254 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 5.84 (d, J=15.0 Hz, 1H), 7.18 (d, J=8.6 Hz, 2H), 7.46 (m, 6H), 7.58 (m, 6H), 8.05 (d, J=15.0 Hz, 1H). HRMS ESI (m/z): Calculated for C21H16O2S ([M+H]+): 333.0871. found: 333.0852.
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][NH:16][C:17](=[S:20])SC)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:21]=[N+:22]=[N-:23].[Na+]>O.C(O)C>[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][N:16]3[C:17](=[S:20])[NH:23][N:22]=[N:21]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CSC(=S)NCCCN1CCN(c2ccccc2)CC1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: S=c1[nH]nnn1CCCN1CCN(c2ccccc2)CC1
Reaction time: 4.5 h
Yield: 25.2 %

Procedure:
To a solution of methyl N-[3-(4-phenyl-1-piperazinyl)propyl]dithiocarbamate (12.9 g) in a mixture of water (20 m) and ethanol (30 m) was added sodium azide (3.6 g). The resulting mixture was refluxed with stirring for 4.5 hours. The reaction mixture was concentrated under reduced pressure. After the addition of water to the residue, the mixture was washed successively with ethyl acetate and diethyl ether and then evaporated. To the residue was added ethanol (100 m) and the mixture was filtered. The filtrate was evaporated under reduced pressure. The residue was recrystallized from isopropyl alcohol twice to give 1-[3-(4-phenyl-1-piperazinyl)propyl]-4,5-dihydro-1H-tetrazole-5-thione (3.2 g), mp. 200° to 205° C.
Reaction SMILES: [ClH:1].[CH2:2]([NH:4][C:5](=[O:30])[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:29])[C@H:12]([CH2:22][CH2:23][CH2:24][NH:25][C:26](=[NH:28])[NH2:27])[NH:13][C:14](=[O:21])[C@H:15]([CH2:17][CH:18]([CH3:20])[CH3:19])[NH2:16])[CH3:3].[CH2:31]([O:38][C:39]([NH:41][C@@H:42]([C:50](O)=[O:51])[CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:40])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O>[ClH:1].[CH2:2]([NH:4][C:5](=[O:30])[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:29])[C@H:12]([CH2:22][CH2:23][CH2:24][NH:25][C:26](=[NH:27])[NH2:28])[NH:13][C:14](=[O:21])[C@H:15]([CH2:17][CH:18]([CH3:19])[CH3:20])[NH:16][C:50](=[O:51])[C@@H:42]([CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[NH:41][C:39]([O:38][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:40])[CH3:3]
Reactant: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CC(C)C
Reactant: O=C(N[C@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Temperature: 23 °C
Reaction time: 72 h

Procedure:
A mixture of the above product g), 900 mg. of Nα -benzyloxycarbonyl-D-phenylalanine [cf. Yajima and Kubo, J. Am. Chem. Soc., 87, 2039 (1965)] and 400 mg. of 1-hydroxybenztriazole is dissolved in 40 ml. of dimethylformamide and then cooled and treated with 700 mg. of dicyclohexylcarbodiimide. The reaction is stirred at 23° C. for three days, filtered and the filtrate evaporated at 50° C. and under reduced pressure. The residue is obtained solid by repeated precipitation from methanol by ether and by ethyl acetate and ether; liquifies 130°-135° C.; [α]D23 -69° (c 1.02, methanol); ultraviolet in methanol λmax 258 E11 5.8.
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:21])[NH:6][C:7](=[O:20])[NH:8][C:9]=1[C:10](=[O:19])[C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].Br[CH2:23][C:24](=[O:27])[CH2:25][CH3:26]>>[CH2:23]([N:8]1[C:9]([C:10](=[O:19])[C:11]2[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:21])[NH:6][C:7]1=[O:20])[C:24](=[O:27])[CH2:25][CH3:26]
Reactant: CCC(=O)CBr
Reactant: Cc1cc(C)cc(C(=O)c2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Product: CCC(=O)Cn1c(C(=O)c2cc(C)cc(C)c2)c(C(C)C)c(=O)[nH]c1=O
Yield: 55 %

Procedure:
5-Isopropyl-6-(3,5-dimethylbenzoyl)-2,4-pyrimidinedione and 1-bromo-2-butanone were reacted by the same way with the example 1 to obtain the titled compound (196 mg, yield: 55%).
Reaction SMILES: Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([CH3:32])[N:27]=[C:26]2[Sn](CCCC)(CCCC)CCCC>CN(C=O)C.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.[Cu]I>[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[N:28]([CH3:32])[N:27]=[C:26]2[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1
Reactant: C[Si](C)(C)CCOCn1cc(C=O)c2nc(Br)cnc21
Reactant: CCCC[Sn](CCCC)(CCCC)c1nn(C)c2ccc(OC)cc12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)c(-c1cnc3c(n1)c(C=O)cn3COCC[Si](C)(C)C)nn2C
Temperature: 90 °C
Reaction time: 2.5 h
Yield: 82.1 %

Procedure:
In a 25 mL round-bottomed flask, 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (439 mg, 1.23 mmol) and 5-methoxy-1-methyl-3-(tributylstannyl)-1H-indazole (556 mg, 1.23 mmol) were dissolved in DMF (3.00 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (71.2 mg, 61.6 μmol) and CuI (46.9 mg, 246 μmol, Eq: 0.20) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 2.5 h. The reaction mixture was concentrated under high vacuum and the residue was purified by chromatography (80 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min) to give 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (443 mg, 1.01 mmol, 82.2%) as a yellow solid. MS (M+H)+=438 (>90% purity); 1H NMR (CDCl3) δ: 10.50 (s, 1H), 9.34 (s, 1H), 8.37 (d, J=2.3 Hz, 1H), 8.30 (s, 1H), 7.39 (d, J=9.1 Hz, 1H), 7.19 (dd, J=9.1, 2.3 Hz, 1H), 5.80 (s, 2H), 4.21 (s, 3H), 4.07 (s, 3H), 3.59-3.73 (m, 2H), 0.91-1.06 (m, 2H), 0.00 (s, 8H).
Reaction SMILES: [CH:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]([O:17][CH2:18][CH:19]([CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28]CCOC(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[OH:20])[CH2:15][CH3:16].[H-].[Na+].[CH3:53]I.CO>C1COCC1>[CH:1]#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]([O:17][CH2:18][CH:19]([CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][OH:28])[O:20][CH3:53])[CH2:15][CH3:16]
Reactant: CI
Reactant: C#CCCCCCCCCCCCC(CC)OCC(O)COCCOCCOCCOC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: C#CCCCCCCCCCCCC(CC)OCC(COCCOCCO)OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 45 %

Procedure:
Then 1.8 g (6.12 millimole) of this epoxy derivative was converted into crude 1-O-(hexadecyn-14-yl)-3-O-[2-(2-trityloxyethoxyethoxy)ethyl]glycerol by following the procedure described in Working Example 62. The crude product was dissolved in 20 ml of THF, to which 367 mg (9.18 millimole) of 60% sodium hydride was added, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added dropwise 1.74 g (12.2 millimole) of methyl iodide in 4 ml of THF over a period of 20 minutes. The reaction mixture was stirred at room temperature overnight, to which was added 1 ml of methanol, and the mixture was concentrated under reduced pressure. The residue was extracted with hexane, and the hexane layer was washed with water, and then hexane was distilled off. To the residue were added 45 ml of dioxane, 30 ml of methanol and 12 ml of 2N hydrochloric acid, and the mixture was stirred at 70° C. for 1 hour. The reaction mixture was cooled, neutralized with saturated aqueous solution of sodium hydrogencarbonate, and concentrated under reduced pressure, and then the residue was extracted with ethyl acetate. The organic layer was washed with water and dried, and the solvent was distilled off. The residue was subjected to silica gel (50 g) column chromatography, and eluted with chloroform-methanol (9:1), to give the above-captioned compound as colorless oil.
Reaction SMILES: [N:1]1([C:7]([NH2:9])=[NH:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:10][C:11]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:12]=1[CH:13]=[C:14]([C:17]#[N:18])[C:15]#[N:16]>>[NH2:18][CH2:17][C:14]1[C:15]([NH2:16])=[N:8][C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[N:9][C:13]=1[C:12]1[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:11]=1[Cl:10]
Reactant: N#CC(C#N)=Cc1ccc(Cl)cc1Cl
Reactant: N=C(N)N1CCOCC1
Product: NCc1c(N)nc(N2CCOCC2)nc1-c1ccc(Cl)cc1Cl

Procedure:
The title compound, MS: m/e=353.9 (M+), was prepared from morpholine-4-carboxamidine and 2-(2,4-dichloro-benzylidene)-malononitrile in analogy to the process described in Example 11 as a solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14](C(OC(C)(C)C)=O)[N:15]=[C:16]([CH3:17])[C:11]3=[C:10]([C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]4)=[CH:27][CH:26]=3)[C:9]=2[C:44]#[N:45])=[C:4]([F:46])[CH:3]=1.[CH3:47][O-].[Na+].C=O.[BH4-].[Na+]>CO.O>[C:44]([C:9]1[C:10]([C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:41])[CH3:42])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)=[C:11]2[C:16]([CH3:17])=[N:15][NH:14][C:12]2=[N:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH3:47])=[CH:3][C:4]=1[F:46])#[N:45]
Reactant: Cc1nn(C(=O)OC(C)(C)C)c2nc(-c3ccc(N)cc3F)c(C#N)c(-c3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3)c12
Reactant: C[O-]
Agent: C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CNc1ccc(-c2nc3[nH]nc(C)c3c(-c3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3)c2C#N)c(F)c1
Yield: 20.8 %

Procedure:
To a solution of 0.20 g (0.32 mmol) of tert-butyl 6-(4-amino-2-fluorophenyl)-4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-5-cyano-3-methyl-1H-pyrazolo[3,4-b]pyridine-1-carboxylate in 40 ml of MeOH are added 0.16 mg (2.9 mmol) of sodium methoxide and 0.10 g (3.2 mmol) of paraformaldehyde. The reaction mixture is refluxed for 2 h. The mixture is then cooled, 0.24 g (6.34 mmol) of sodium borohydride is added, and the mixture is refluxed for 1 h. The mixture is then cooled, diluted with iced water, then extracted with dichloromethane. The organic phase is dried over magnesium sulfate, filtered, and concentrated. The solid obtained is then purified by chromatography on silica (methanol gradient in dichloromethane: 1 to 2%) to give 0.036 g (18%) of tert-butyl 4-(4-(5-cyano-6-(2-fluoro-4-(methylamino)phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)piperazine-1-carboxylate in the form of yellow crystals. Deprotection of the piperazine following general procedure E2 gives 0.02 g (68%) of 6-(2-fluoro-4-(methylamino)phenyl)-3-methyl-4-(4-(piperazine-1-yl)phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile hydrochloride in the form of orange crystals.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([CH3:16])=[CH:14][C:13]([O:17][CH:18]([C:22]3[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=3)[CH:19]([CH3:21])[CH3:20])=[CH:12][C:11]=2[CH3:31])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:39][O:40][C:41](=[O:46])[CH:42]([OH:45])[CH2:43][NH2:44].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:39][O:40][C:41](=[O:46])[CH:42]([OH:45])[CH2:43][NH:44][C:26](=[O:27])[C:25]1[CH:29]=[CH:30][C:22]([CH:18]([O:17][C:13]2[CH:14]=[C:15]([CH3:16])[C:10]([C:7]3[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=3)=[C:11]([CH3:31])[CH:12]=2)[CH:19]([CH3:21])[CH3:20])=[CH:23][CH:24]=1
Reactant: COC(=O)C(O)CN
Reactant: Cc1cc(OC(c2ccc(C(=O)O)cc2)C(C)C)cc(C)c1-c1ccc(C(C)C)cc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)C(O)CNC(=O)c1ccc(C(Oc2cc(C)c(-c3ccc(C(C)C)cc3)c(C)c2)C(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 4-[1-(4′-isopropyl-2,6-dimethyl-biphenyl-4-yloxy)-2-methyl-propyl]-benzoic acid (150 mg, 0.36 mmol) in methylene chloride (4 mL) is added triethyl amine (0.15 mL, 1.08 mmol), DMAP (5.0 mg), 3-Amino-2-hydroxy-propionic acid methyl ester (83 mg, 0.54 mmol) and EDCI (208 mg, 1.08 mmol) at room temperature. The reaction mixture is stirred at room temperature overnight, loaded on silica gel, eluted with eluted with hexanes with a gradient from 0% of ethyl acetate to 100% of ethyl acetate giving the titled compound (150 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].Cl[C:25](Cl)([O:27][C:28](=[O:34])OC(Cl)(Cl)Cl)Cl.[CH:36]1(O)[CH2:42][CH2:41]C[CH2:39][CH2:38][CH2:37]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:28](=[O:34])[O:27][CH:25]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:42][CH2:41]1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2ncnc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Reactant: OC1CCCCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc2ncnc(Oc3ccc(NC(=O)OC4CCCCCC4)c(Cl)c3)c2cc1OC
Yield: 84.4 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-cycloheptanol (26 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (60 mg, yield 73%).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:7][N:6]1[C:19](=O)[CH2:20][C:21](=[O:23])[CH3:22])=[O:4].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:34])=CC=1>>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:7][N:6]1[C:19](=[S:34])[CH2:20][C:21](=[O:23])[CH3:22])=[O:4]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2)CN1C(=O)CC(C)=O
Product: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccccc2)CN1C(=S)CC(C)=O

Procedure:
In analogy to the procedure described in example 192 g, (2S,4R)-4-benzenesulfonyl-1-(3-oxo-butyryl)-pyrrolidine-2-carboxylic acid methyl ester was reacted with Lawesson's reagent to give the title compound as red oil.
Reaction SMILES: [N:1]1[N:2]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:3]=[C:4]2[C:9]=1[CH:8]=[CH:7][CH:6]=[CH:5]2.[I-].[Na+].[H-].[Na+].Cl[CH2:22][CH2:23][CH2:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1>CN(C)C=O>[N:25]1([CH2:24][CH2:23][CH2:22][O:16][C:13]2[CH:14]=[CH:15][C:10]([N:2]3[CH:3]=[C:4]4[C:9]([CH:8]=[CH:7][CH:6]=[CH:5]4)=[N:1]3)=[CH:11][CH:12]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1
Reactant: ClCCCN1CCCC1
Reactant: Oc1ccc(-n2cc3ccccc3n2)cc1
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc2nn(-c3ccc(OCCCN4CCCC4)cc3)cc2c1
Temperature: 85 °C
Yield: 12 %

Procedure:
To a solution of 4-Indazol-2-ylphenol (28 mg, 0.13 mmol) and sodium iodide (6 mg, 0.04 mmol) in N,N-dimethylformamide (3 mL) was added sodium hydride (8.0 mg, 60% in mineral oil, 0.2 mmol) followed by 1-(3-chloropropyl)pyrrolidine (30 mg, 0.20 mmol). After the reaction was heated at 85° C. overnight and allowed to cool, it was partitioned between water and methylene chloride. The organic layer was dried (MgSO4), concentrated and purified by semi-prep LC-MS to give 5.0 mg of the desired indazole. LC-MS (C20H23N3O calc'd 321) m/z 322 (M+H); 1H NMR (300 MHz, CDCl3) δ 8.33 (s, 1H), 7.81-7.77 (m, 3H), 7.71 (d, J=8.7 Hz, 1H), 7.34-7.29 (m, 1H), 7.14-7.09 (m, 1H), 7.05-7.02 (m, 2H), 4.10 (t, J=6.6 Hz, 2H), 2.72 (t, J=7.2 Hz, 2H), 2.63 (m, 4H), 2.08 (quint, J=6.3 Hz, 2H), 1.86-1.81 (m, 4H).
Reaction SMILES: [OH:1][CH:2]([CH2:10][OH:11])[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[Cl:12][C:13]1[N:14]=[N:15][C:16](Cl)=[CH:17][CH:18]=1>C(O)(C)C>[Cl:12][C:13]1[N:14]=[N:15][C:16]([N:7]2[CH2:8][CH2:9][N:4]([CH2:3][CH:2]([OH:1])[CH2:10][OH:11])[CH2:5][CH2:6]2)=[CH:17][CH:18]=1
Reactant: Clc1ccc(Cl)nn1
Reactant: OCC(O)CN1CCNCC1
Solvent: CC(C)O
Product: OCC(O)CN1CCN(c2ccc(Cl)nn2)CC1

Procedure:
Grams 32 of 1-(2,3-dihydroxypropyl)piperazine and 15 g of 3,6-dichloropyridazine in 700 ml isopropanol were refluxed for 24 hours. The reaction mixture was settled, the solid undissolvable removed and the solution evaporated to dryness. The so obtained residue was purified on column eluting with chloroform:methanol (9:1). Grams 2.1 of 3-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]propane-1,2-diol, which, recrystallized from acetone, melted at 126°-128° C.
Reaction SMILES: [CH:1]1([C:4](Cl)=[O:5])[CH2:3][CH2:2]1.[O:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12]1[N:17]=[C:16]([NH2:18])[CH:15]=[N:14][C:13]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[N:20]=1>N1C=CC=CC=1>[O:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12]1[N:17]=[C:16]([NH:18][C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:5])[CH:15]=[N:14][C:13]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[N:20]=1
Reactant: O=C(Cl)C1CC1
Reactant: Cc1nccc(-c2ncc(N)nc2-c2ccco2)n1
Solvent: c1ccncc1
Product: Cc1nccc(-c2ncc(NC(=O)C3CC3)nc2-c2ccco2)n1
Temperature: 80 °C
Reaction time: 3 h
Yield: 24.9 %

Procedure:
Cyclopropanecarbonyl chloride (0.028 mL, 0.30 mmol) was added to a stirred solution of 6-(2-furyl)-5-(2-methylpyrimidin-4-yl)pyrazin-2-amine (Example 9, 38 mg, 0.15 mmol) in pyridine (0.5 mL). The mixture was heated to 80° C. in a sealed tube and stirred for 3 h. The crude reaction was concentrated to dryness and the residue was diluted with ethyl acetate and washed with aqueous sodium bicarbonate 4%. The organic layer was dried (Na2SO4) and evaporated. The residue was purified with flash silica gel chromatography (30% ethyl acetate in hexanes). Concentration in vacuo of the product-rich fractions provided the titled compound as a pale-yellow solid (12 mg, 25%).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:21]=[CH:20][C:13]([O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.CO>C1(C)C=CC=CC=1>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([O:14][CH:15]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:16]([O:18][CH3:19])=[O:17])=[CH:20][CH:21]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: BrCc1ccccc1
Reactant: COC(=O)COc1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: CO
Solvent: Cc1ccccc1
Product: COC(=O)C(Cc1ccccc1)Oc1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Temperature: 0 °C
Yield: 41.7 %

Procedure:
A solution of 1.00 g (3.23 mmol) of the product of Step B dissolved in 4 mL of toluene was stirred under a N2 atmosphere and cooled to 0° C. with an ice-water bath. To this solution was added 9.68 mL (4.85 mmol) of a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene. After a 15 minute interval, 0.46 mL (3.88 mmol) of benzyl bromide was added and the reaction mixture was allowed to warm to room temperature and stirred 1 hour. Several milliliters of methanol were added to consume excess base, and the reaction was partitioned between ethyl acetate and 1N HCl. The organic layer was separated, washed with saturated NaHCO3, brine, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with 15% ethyl acetate/hexane to afford 0.540 g (42%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([CH:9]([OH:11])[CH3:10])[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[I:18]I>O>[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([I:18])[CH:5]=[C:4]([CH:9]([OH:11])[CH3:10])[N:3]=1
Reactant: CC(O)c1ccc(O)c(Cl)n1
Reactant: II
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CC(O)c1cc(I)c(O)c(Cl)n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 62.3 %

Procedure:
2-Chloro-3-hydroxy-6-(1-hydroxyethyl)-pyridine (4.5 g, 23.6 mmole) is suspended in 70 ml water in a 200 ml one neck round bottom flask. The suspension is treated successively with potassium carbonate (6.5 g, 47.2 mmole) and iodine (12.0 g, 47.2 mmole) and the reaction mixture is stirred 4 h at room temperature. The excess iodine is quenched with saturated sodium thiosulfate and the pH of the reaction mixture is adjusted to 3 with 10% hydrochloric acid. The solid is collected, washed with water, and is taken up in ethyl acetate. The organic layer is dried over magnesium sulfate and is concentrated in vacuo to a yellow solid. The solid is washed with chloroform and is dried to provide 4.4 g (62%) of 2-chloro-3-hydroxy-4-iodo-6-(1-hydroxyethyl)-pyridine.
Reaction SMILES: C[O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([C:24](=[O:28])[C:25]([NH2:27])=[O:26])=[C:9]([CH3:23])[N:10]2[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.[OH-].[Na+].CO.C(OCC)(=O)C>O>[NH2:27][C:25](=[O:26])[C:24]([C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[CH:14][C:6]=2[O:5][CH2:4][C:3]([OH:29])=[O:2])[N:10]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[C:9]=1[CH3:23])=[O:28]
Reactant: COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: O
Product: Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81.2 %

Procedure:
A mixture of 767 mg (1.9 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester, 10 mL of 1N NaOH and 30 mL of MeOH was heated to maintain reflux for 0.67 hours, cooled to room temperature and stirred 1 hour. Ethyl acetate and water were added and the aqueous layer separated, made acidic to pH 2-3 with 1N HCl and the mixture extracted with ethyl acetate two times. The combined ethyl acetate extracts were dried (MgSO4) and concentrated. The remaining solid was washed with a small volume of ethyl acetate to give 593 mg (81% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid, mp, 244°-247° C.