Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH2:28][CH:29]1[CH2:33][CH2:32][NH:31][CH2:30]1)[C:3]1[S:4][C:5]2[CH:11]=[C:10]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)=[CH:17][CH:16]=3)=[O:14])[CH:9]=[CH:8][C:6]=2[N:7]=1.[CH:34](=O)[CH3:35].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(Cl)Cl>[CH2:34]([N:31]1[CH2:32][CH2:33][CH:29]([CH2:28][N:2]([CH3:1])[C:3]2[S:4][C:5]3[CH:11]=[C:10]([NH:12][C:13]([C:15]4[CH:16]=[CH:17][C:18]([C:21]5[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=5)=[CH:19][CH:20]=4)=[O:14])[CH:9]=[CH:8][C:6]=3[N:7]=2)[CH2:30]1)[CH3:35]
Reactant: CN(CC1CCNC1)c1nc2ccc(NC(=O)c3ccc(-c4ccc(F)cc4)cc3)cc2s1
Reactant: CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCN1CCC(CN(C)c2nc3ccc(NC(=O)c4ccc(-c5ccc(F)cc5)cc4)cc3s2)C1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 78.2 %

Procedure:
Place 4′-fluoro-biphenyl-4-carboxylic acid [2-(methyl-pyrrolidin-3-ylmethyl-amino)-benzothiazol-6-yl]-amide (123 mg, 0.267 mmol) in THF (3 mL) and cool to 0° C. Add acetaldehyde (0.040 mL, 0.716 mmol) and sodium triacetoxyborohydride (88 mg, 0.415 mmol). Stir at 0° C. for 10 min. Dilute with DCM and wash with 1N NaOH. Collect the organic layer and chromatograph (silica gel, eluting with 10% 2M NH3 in MeOH:DCM) to yield 102 mg (78%) of the title compound: mass spectrum (ion-spray): (m/z)=489.0 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[C:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[C:4]=2[CH:3]=1.[CH2:22]1[O:24][CH2:23]1>CO>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[C:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][OH:24])[CH2:18][CH2:17]3)[C:4]=2[CH:3]=1
Reactant: C1CO1
Reactant: Clc1ccc2c(c1)C(=C1CCNCC1)c1ccccc1S2
Solvent: CO
Product: OCCN1CCC(=C2c3ccccc3Sc3ccc(Cl)cc32)CC1
Reaction time: 8 h

Procedure:
To a solution of 13.2 g. (0.0318 m.) of 4-(2-chloro-9-thioxanthenylidene)-piperidine in 50 ml. of methanol at 50° C. is added a solution of 2.2 g. (0.0383 m.) of ethylene oxide in 30 ml. of methanol over ten minutes and the mixture is refluxed for one and one-half hours. After standing overnight at room temperature, the reaction mixture is filtered to yield 4-(2-chloro-9-thioxanthenylidene)-1-(β-hydroxyethyl)-piperidine, m.p. 178°-180° C.
Reaction SMILES: C(P(CCCC)CCCC)CCC.[CH3:14][N:15]1[C:19]([CH2:20][OH:21])=[CH:18][C:17]([C:22]([F:25])([F:24])[F:23])=[N:16]1.[CH2:26]([O:28][C:29](=[O:41])[CH2:30][C:31]1[C:35]2[CH:36]=[CH:37][C:38](O)=[CH:39][C:34]=2[S:33][CH:32]=1)[CH3:27].C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1>[CH2:26]([O:28][C:29](=[O:41])[CH2:30][C:31]1[C:35]2[CH:36]=[CH:37][C:38]([O:21][CH2:20][C:19]3[N:15]([CH3:14])[N:16]=[C:17]([C:22]([F:23])([F:24])[F:25])[CH:18]=3)=[CH:39][C:34]=2[S:33][CH:32]=1)[CH3:27]
Reactant: CCOC(=O)Cc1csc2cc(O)ccc12
Reactant: Cn1nc(C(F)(F)F)cc1CO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: CCOC(=O)Cc1csc2cc(OCc3cc(C(F)(F)F)nn3C)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.5 %

Procedure:
To a mixture of tri-n-butylphosphine (0.165 mL), (1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanol (110 mg), ethyl(6-hydroxy-1-benzothiophen-3-yl)acetate (120 mg), and THF (5.0 mL) was added ADDP (167 mg) at room temperature. The mixture was stirred at room temperature under nitrogen atmosphere overnight. The mixture was concentrated. To the residue was added IPE and the precipitate was filtered off. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH, EtOAc/hexane) and then silica gel column chromatography (EtOAc/hexane) to give the title compound (173 mg). The solid was crystallized from EtOH-hexane to give the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][NH:10][C:11]([NH:13][CH2:14][CH:15](OCC)OCC)=[O:12])([CH3:4])([CH3:3])[CH3:2].Cl.[OH-].[K+]>CO.O>[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][N:10]1[CH:15]=[CH:14][NH:13][C:11]1=[O:12])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(CNC(=O)NCCNC(=O)OC(C)(C)C)OCC
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)NCCn1cc[nH]c1=O
Reaction time: 8 h
Yield: 54.7 %

Procedure:
Dissolve {2-[3-(2,2-diethoxy-ethyl)-ureido]-ethyl}-carbamic acid tert-butyl ester (6.5 g, 20.35 mmol) in methanol (75 mL) and water (40 mL). To the reaction mixture add HCl (0.4 N, 50 mL) dropwise over 30 min. Stir the mixture overnight and neutralize by adding KOH (0.4 M, 50 mL), and concentrate in vacuo. Extract the residue in chloroform and wash with saturated aqueous sodium chloride, dry over MgSO4, filter and remove solvent on a rotovap to give a crude white solid. Purify by column chromatography 1% to 10% MeOH in dichloromethane to afford the pure product as a white solid (2.53 g, 11.13 mmol). GCMS (EI) m/z 227 M+.
Reaction SMILES: [CH3:1][N:2]1[CH2:11][CH2:10][C:9]2[C:4](=[C:5](N)[CH:6]=[CH:7][CH:8]=2)[CH2:3]1.[BrH:13].N([O-])=O.[Na+].[OH-].[Na+]>O.Br.O.C(OCC)(=O)C>[Br:13][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:4]=1[CH2:3][N:2]([CH3:1])[CH2:11][CH2:10]2
Reactant: Br
Reactant: CN1CCc2cccc(N)c2C1
Agent: O=N[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: CN1CCc2cccc(Br)c2C1
Temperature: 0 °C

Procedure:
Into a 50 mL 3-necked round bottom flask (named A), was placed 2-methyl-1,2,3,4-tetrahydroisoquinolin-8-amine (500 mg, 3.08 mmol). This was followed by the addition of a solution of HBr (5 mL) in H2O (5 mL), which was added dropwise with stirring, while cooling to a temperature of 0° C. To the above was added NaNO2 (230 mg, 3.33 mmol) in several batches, while cooling to a temperature of 0° C. and the mixture was stirred for 30 mins at that temperature. Then into another 50 mL 3-necked round bottom flask (named B), was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of CuBr (550 mg, 3.83 mmol) in HBr/H2O (3 mol/L) (10 mL), while cooling to a temperature of 0° C. The mixture was stirred for 10 minutes. Then was followed by the addition of the reaction solution of flask A with dropwise while the temperature was maintained at 0° C. The resulting solution was allowed to react, with stirring, for 30 minutes while the temperature was maintained at 0° C. The resulting solution was allowed to react, with stirring, for an additional 2 hours at room temperature. The reaction progress was monitored by TLC(ethyl acetate:petroleum ether=1:1). Adjustment of the pH to 9 was accomplished by the addition of NaOH (10%). The resulting solution was extracted three times with 50 mL of CH2Cl2 and the organic layers combined and dried over K2CO3. A filtration was performed. The filtrate was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluting through a column with a 1:1 ethyl acetate; petroleum ether solvent system. This resulted in 0.45 g (65%) of 8-bromo-2-methyl-1,2,3,4-tetrahydroisoquinoline as light yellow oil.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[CH2:10][C:11]([OH:13])=[O:12].S(Cl)(Cl)=O.[CH3:18]O>>[CH2:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1][CH:2]1[CH2:10][C:11]([O:13][CH3:18])=[O:12]
Reactant: O=C(O)CC1Cc2ccccc2C1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)CC1Cc2ccccc2C1
Yield: 100 %

Procedure:
Under nitrogen atmosphere, 2-(2,3-dihydro-1H-inden-2-yl)acetic acid (Lanc, 19.6 g, 111 mmol) was dissolved in methanol (100 mL) and cooled in an ice bath. Thionyl chloride (9.7 mL, 133 mmol) was slowly added dropwise thereto under stirring. After completing the dropwise addition, the ice bath was removed and the reaction solution was additionally stirred for 30 minutes. Upon the completion of the reaction, the reaction solution was added in small portions to ice-cold sodium bicarbonate solution under stirring. The reaction mixture was extracted twice with ethyl acetate, and the obtained organic layer was washed once with water, dried over anhydrous magnesium sulfate, and the reaction solution was concentrated to obtain the target compound (21.2 g, Yield 100%).
Reaction SMILES: [C:1]([C:3]1[C@@H:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=2[S:17]([CH3:20])(=[O:19])=[O:18])[N:7]([C:21](OC2C=CC([N+]([O-])=O)=CC=2)=[O:22])[C:6](=[O:33])[N:5]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)[C:4]=1[CH3:44])#[N:2].[NH2:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][OH:51]>C(#N)C>[C:1]([C:3]1[C@@H:8]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=2[S:17]([CH3:20])(=[O:19])=[O:18])[N:7]([C:21]([NH:45][CH2:46][CH2:47][O:48][CH2:49][CH2:50][OH:51])=[O:22])[C:6](=[O:33])[N:5]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:42])([F:43])[F:41])[CH:35]=2)[C:4]=1[CH3:44])#[N:2]
Reactant: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2S(C)(=O)=O)N(C(=O)Oc2ccc([N+](=O)[O-])cc2)C(=O)N1c1cccc(C(F)(F)F)c1
Reactant: NCCOCCO
Solvent: CC#N
Product: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2S(C)(=O)=O)N(C(=O)NCCOCCO)C(=O)N1c1cccc(C(F)(F)F)c1

Procedure:
According to the General Procedure 1, 4-nitrophenyl (6S)-5-cyano-6-[4-cyano-2-(methylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-3,6-dihydropyrimidine-1(2H)-carboxylate (46.5 mg, 0.074 mmol; Example 6A) was reacted with 2-(2-aminoethoxy)ethanol (23.4 mg, 0.223 mmol) in acetonitrile (1 ml) to give the target compound (30 mg, 68% of theory).
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[OH:12].[H-].[Na+].[CH3:15]I>C1COCC1>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:12][CH3:15]
Reactant: Oc1ccc2ccccc2c1Br
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc2ccccc2c1Br
Temperature: 25 °C

Procedure:
1-Bromo-2-naphthol (2.0 g, 8.97 mmol) was dissolved in THF (20 mL), and the solution was cooled to 0 deg in an ice bath. NaH was added thereto (60% dispersion of in mineral oil, 430 mg 10.8 mmol), followed by MeI (1.2 mL, 19.6 mmol) as bubbling subsided. The reaction mixture was heated to reflux overnight, cooled to room temperature, and water added dropwise thereto until bubbling subsided. The reaction mixture was diluted with EtOAc, and the organic layer was washed once each with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10% to 50% EtOAc/hexanes to afford 1-bromo-2-methoxynaphthalene as a solid. LC/MS (ES MS, M+H+ found: 238) and proton NMR (400 MHz, CDCl3) δ 4.04 (s, 3H), 7.28 (d, J=9 Hz, 1H), 7.42 (t, J=7 Hz, 1H), 7.58 (t, J=6.8 Hz, 1H), 7.8 (dd, J=9 Hz, 2H), 8.2 (d, J=8.6 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[CH2:6][NH:7][CH3:8].ClC([O:17][C:18]([Cl:21])(Cl)Cl)=O>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[CH2:6][N:7]([CH3:8])[C:18]([Cl:21])=[O:17]
Reactant: CNCc1ccc(OC)c(OC)c1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: COc1ccc(CN(C)C(=O)Cl)cc1OC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.00 g (5.52 mmol) of 3,4-dimethoxybenzyl-N-methylamine (obtainable by reductive amination from 3,4-dimethoxybenzaldehyde) are dissolved in 20 ml of anhydrous pyridine. 0.60 g (0.37 mmol, 3.04 mmol) of trichloromethyl chloroformate (“diphosgene”) is added, and the mixture is left to stir at room temperature overnight. The solution is employed without workup directly in the next stage.
Reaction SMILES: C(O)(=O)C.[CH2:5]([O:7][C:8]1[N:13]=[C:12]([CH:14]=O)[CH:11]=[CH:10][CH:9]=1)[CH3:6].[CH2:16]([O:18][C:19]([C:21]1[NH:22][CH:23]=[CH:24][C:25]=1[NH2:26])=[O:20])[CH3:17].[BH3-]C#N.[Na+]>C(O)C>[CH2:16]([O:18][C:19]([C:21]1[NH:22][CH:23]=[CH:24][C:25]=1[NH:26][CH2:14][C:12]1[CH:11]=[CH:10][CH:9]=[C:8]([O:7][CH2:5][CH3:6])[N:13]=1)=[O:20])[CH3:17]
Reactant: CCOC(=O)c1[nH]ccc1N
Reactant: CCOc1cccc(C=O)n1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)c1[nH]ccc1NCc1cccc(OCC)n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 45.5 %

Procedure:
Acetic acid (0.3 mL) was added to 6-ethoxy-pyridine-2-carbaldehyde (0.59 g, 3.9 mmol) and 3-amino-1H-pyrrole-2-carboxylic acid ethyl ester (0.30 g, 1.9 mmol) in ethanol (10 mL). After 1.5 h, NaCNBH3 (0.24 g, 3.9 mmol) was added, and the resulting mixture was stirred at ambient temperature for 19 h. The solvent was removed in vacuo, ethyl acetate was added to the residue, and insoluble material was removed by filtration. The filtrate was concentrated and the crude product was purified by flash column chromatography (heptane/ethyl acetate gradient; 0 to 35% ethyl acetate), obtaining 0.25 g (45%) of the title product as a solid.
Reaction SMILES: [F:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([CH:8]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH2:9][C:10](OCC)=[O:11])=O)=[CH:4][CH:3]=1.O.[NH2:24][NH2:25]>C(O)C>[F:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]2[CH:8]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)[CH2:9][C:10](=[O:11])[NH:24][N:25]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)CC(C(=O)c1ccc(F)cc1)c1ccncc1
Reactant: NN
Solvent: CCO
Solvent: O
Product: O=C1CC(c2ccncc2)C(c2ccc(F)cc2)=NN1

Procedure:
A solution of ethyl 3-(4-fluorobenzoyl)-3-(4-pyridyl)-propionate (1.0 g, 3.32 mmol) and hydrazine monohydrate (1 ml, 20.6 mmol) in ethanol (1 ml) was refluxed for 2.5 h. The solvent and hydrazine monohydrate were evaporated. The remainder was taken up in n-butanol and the mixture was heated at reflux for 45 min. Evaporation was followed by column chromatography on silica gel (3-7.5% methanol/dichloromethane) to provide the title compound. MS (m/z): 270.2 (M+H)+; C15H12FN3O requir. 269.3.
Reaction SMILES: [CH:1](=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH2:8](Cl)[CH:9]=[CH2:10].O.O.[Sn](Cl)Cl>[Cu].O>[OH:7][CH:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:10][CH:9]=[CH2:8]
Reactant: C=CCCl
Reactant: CCCCCC=O
Agent: [Cu]
Agent: Cl[Sn]Cl
Solvent: O
Product: C=CCC(O)CCCCC
Temperature: 30 °C
Reaction time: 8 h

Procedure:
3500 ml water, 200 g hexanal (2 mol) and 305 g allyl chloride (4 mol), 900 g tin(II) chloride dihydrate (2 mol) and 25 g copper powder (0.4 mol) was added into a 61 flask. The reaction mixture was stirred at ca. 30° C. for 8 h. The organic phase was separated by decantation or centrifugation and the crude raw product distilled in vacuo to give 4-hydroxy-1-nonene. MS: m/z 141 (M-1), 101 (M-C3H5), 124 (M-18), 83 (101-18), 55 (83-C2H4).
Reaction SMILES: [CH:1]1([C:4]2[CH:9]=[CH:8][C:7]([N:10]3[CH2:14][CH2:13][C:12]4([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]4)[C:11]3=[O:20])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.S(Cl)([Cl:24])(=O)=O.CCN(CC)CC>C(Cl)(Cl)Cl>[Cl:24][C:6]1[CH:5]=[C:4]([CH:1]2[CH2:3][CH2:2]2)[CH:9]=[CH:8][C:7]=1[N:10]1[CH2:14][CH2:13][C:12]2([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[C:11]1=[O:20]
Reactant: O=S(=O)(Cl)Cl
Reactant: O=C1N(c2ccc(C3CC3)cc2)CCC12CCNCC2
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: O=C1N(c2ccc(C3CC3)cc2Cl)CCC12CCNCC2
Yield: 30.8 %

Procedure:
A mixture of 0.275 g (1 mmol) 2-(4-Cyclopropyl-phenyl)-2,8-diaza-spiro[4.5]decan-1-one. 1.57 g (11.3 mmol) sulfuryl chloride and 0.154 g (1.52 mmol) NEt3 in 50 mL CHCl3 was stirred at room temperature. After evaporation of the volatiles the residue was taken up in DMF and subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 94 mg (30%) of the title compound as light yellow gum. MS m/e: 305.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([O:17][Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20])[CH2:13][N+:14]([O-])=O)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Cl-].[NH4+]>CCO.O.[Fe]>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([O:17][Si:18]([CH2:19][CH3:20])([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:13][NH2:14])=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: CC[Si](CC)(CC)OC(C[N+](=O)[O-])c1c(Cl)cnc2ccccc12
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: CC[Si](CC)(CC)OC(CN)c1c(Cl)cnc2ccccc12
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To a clear yellow solution of 3-chloro-4-(2-nitro-1-((triethylsilyl)oxy)ethyl)quinoline (0.511 g, 1.39 mmol) in EtOH (7.96 mL) and water (1.99 mL) at room temperature was added iron powder (0.778 g, 13.9 mmol) and ammonium chloride (0.745 g, 13.9 mmol). The dark brown mixture was stirred and heated at 60° C. After 4 h, the mixture was cooled to room temperature and filtered through a celite pad and washed the pad with MeOH (3×30 mL). The combined filtrates were concentrated in vacuo. The residue was partitioned between EtOAc (100 mL) and water (50 mL). The mixture (pH ˜4.0) washed with saturated aqueous NaHCO3 (1×50 mL), water (1×50 mL), and brine (1×50 mL), dried over anhydrous Na2SO4, concentrated in vacuo, and dried under high vacuum to give 2-(3-chloroquinolin-4-yl)-2-((triethylsilyl)oxy)ethanamine (A275-6) as a yellow syrup. 1H NMR (400 MHz, DMSO-d6) δ 8.84 (1H, s), 8.72 (1H, d, J=8.2 Hz), 8.04 (1H, dd, J=8.4, 1.0 Hz), 7.76 (1H, ddd, J=8.4, 6.9, 1.4 Hz), 7.64 (1H, ddd, J=8.5, 7.0, 1.3 Hz), 5.52 (1H, dd, J=7.6, 5.5 Hz), 3.16 (1H, dd, J=13.0, 7.9 Hz), 2.88 (1H, dd, J=13.0, 5.4 Hz), 1.74 (1H, br. s.), 0.71-0.80 (1H, m), 0.71-0.80 (9H, m), 0.37-0.57 (6H, m); LCMS (ESI) m/z 337.1 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][C:14]([C:16]([OH:18])=[O:17])=[CH:13][CH:12]=3)[CH:9]=2)[NH:4][N:3]=1.[C:19]1(C)C=CC(S(O)(=O)=O)=C[CH:20]=1>C(O)C>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:13][CH:12]=3)[CH:9]=2)[NH:4][N:3]=1
Reactant: Nc1n[nH]c2ccc(-c3ccc(C(=O)O)o3)cc12
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: CCOC(=O)c1ccc(-c2ccc3[nH]nc(N)c3c2)o1
Yield: 26.9 %

Procedure:
100 mg of 5-(3-amino-1H-indazol-5-yl)furan-2-carboxylic acid and 78 mg of p-toluenesulfonic acid are heated at 75° C. for 3 days in 5 ml of ethanol. The batch is evaporated, water is added, and the mixture is neutralised. The mixture is extracted three times with EA, the combined org. phases are washed with water, dried and evaporated to dryness. Purification by RP chromatography gives 30 mg of ethyl 5-(3-amino-1H-indazol-5-yl)furan-2-carboxylate, corresponding to a yield of 27%.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[C@:5](O)([CH3:23])[C@@H:6]([C@H:16]1[CH2:20][O:19][C:18]([CH3:22])([CH3:21])[O:17]1)[O:7][C:8](=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:2].CCN(S(F)(F)[F:32])CC.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:1]([O:3][C:4](=[O:25])[C@@:5]([F:32])([CH3:23])[C@@H:6]([C@H:16]1[CH2:20][O:19][C:18]([CH3:22])([CH3:21])[O:17]1)[O:7][C:8](=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:2]
Reactant: CCOC(=O)[C@@](C)(O)[C@H](OC(=O)c1ccccc1)[C@H]1COC(C)(C)O1
Reactant: CCN(CC)S(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)[C@](C)(F)[C@H](OC(=O)c1ccccc1)[C@H]1COC(C)(C)O1
Temperature: 25 °C
Reaction time: 3 h
Yield: 68 %

Procedure:
To a solution of compound 43 (36 mg, 0.102 mmol) in anhydrous THF (1.5 mL) is added DAST or Deoxofluor (0.08 mL, 0.68 mmol) at 0° C. under argon. The reaction mixture is stirred at room temperature for 3 h, then cooled down to 0° C., and carefully treated with cold saturated NaHCO3 solution (2 mL). The organic layer is dried over Na2SO4 and concentrated to dryness. The residue is purified by silica gel column chromatography with 1-3% EtOAc in hexanes to give 44 (24.6 mg, 68%) as a syrup. HR-FAB MS; Obsd: m/z 361.1621. Calcd for C18H23O6FLi: m/z 361.1639 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][CH2:9][N:10]2C(=O)C3C(=CC=CC=3)C2=O)=[C:6]([NH:21][C@@H:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)[N:5]=[CH:4][N:3]=1.O.NN>C(O)C>[NH2:10][CH2:9][CH2:8][C:7]1[C:6]([NH:21][C@@H:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23]2)=[N:5][CH:4]=[N:3][C:2]=1[Cl:1]
Reactant: O=C1c2ccccc2C(=O)N1CCc1c(Cl)ncnc1N[C@H]1CCc2ccccc21
Agent: NN
Solvent: CCO
Solvent: O
Product: NCCc1c(Cl)ncnc1N[C@H]1CCc2ccccc21
Yield: 49.9 %

Procedure:
2-(2-{4-chloro-6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-5-yl}ethyl)-1H-isoindole-1,3(2H)-dione (3.50 g, 8.32 mmol) was suspended in ethanol (102 mL) and hydrazine hydrate (1.62 mL, 33.3 mmol) was added. The mixture was heated to reflux for 1 hour. At that time, LCMS indicated complete conversion. The mixture was cooled to 23 OC, crystals were filtered off, the residue was evaporated in vacuo and purified using chromatography on silica gel using gradient 0 to 20% MeOH in methylene chloride to afford the title compound (1.20 g, 50%). LC/MS: Rt=1.29 min, ES+ 289 (AA standard).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:2]C.C1C[O:24]CC1>O.[Os](=O)(=O)(=O)=O>[O:24]=[CH:2][CH2:1][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]
Reactant: C1CCOC1
Reactant: CC=Cc1ccc(OC)cc1CCC(=O)OC(C)(C)C
Agent: O=[Os](=O)(=O)=O
Solvent: O
Product: COc1ccc(CC=O)c(CCC(=O)OC(C)(C)C)c1
Temperature: 25 °C
Yield: 43 %

Procedure:
To a solution of tert-butyl 3-(2-propeny-5-methoxyphenyl)propionate (7.2 g, 26 mmol) in THF (60 mL) and H2O (30 mL) were added NaO4 (9.8 g, 46 nmmol) and 4% osmium tetroxide (1 mL). After stirring at RT, the mixture was filtered and the filtrate was diluted with ether. The combined extracts were dried and evaporated to give the crude product which was flash chromatographed to give the titled compound (3.0 g; 43% yield).
Reaction SMILES: CON(C)[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([CH3:18])=[C:12]([CH3:17])[CH:13]=2)[N:8]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=2)[CH:7]=1)=[O:5].[F:28][C:29]1[CH:30]=[C:31]([Mg]Br)[CH:32]=[CH:33][C:34]=1[O:35][CH3:36]>C1COCC1>[F:28][C:29]1[CH:30]=[C:31]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[C:4]([C:6]1[C:15](=[O:16])[C:14]2[C:9](=[N:10][C:11]([CH3:18])=[C:12]([CH3:17])[CH:13]=2)[N:8]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[N:21]=2)[CH:7]=1)=[O:5]
Reactant: CON(C)C(=O)c1cn(Cc2cccc(C)n2)c2nc(C)c(C)cc2c1=O
Reactant: COc1ccc([Mg]Br)cc1F
Solvent: C1CCOC1
Product: COc1ccc(C(=O)c2cn(Cc3cccc(C)n3)c3nc(C)c(C)cc3c2=O)cc1F
Yield: 49.8 %

Procedure:
Experimental conditions analogous to those described for Step 6 of Example 60 were used with 100 mg (0.273 mmol) of 6,7-Dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid methoxy-methyl amide, 1.2 mL (0.60 mmol, 0.5 M in tetrahydrofuran) of 3-fluoro-4-methoxyphenylmagnesium bromide and 1.2 mL of THF. The crude product was purified by flash column chromatography using a gradient of 20-100% ethyl acetate in hexane and further purified on the reverse phase HPLC with a C18 column, gradient of 20-70% acetonitrile—0.1% TFA to yield 58.7 mg 3-(3-Fluoro-4-methoxy-benzoyl)-6,7-dimethyl-1-(6-methyl-pyridin-2-ylmethyl)-1H-[1,8]naphthyridin-4-one. LC-MSD, m/z for C25H22FN3O3 [M+H]: 432.16 LC retention time on HPLC, C18 column gradient 20-95% acetonitrile with 0.1% TFA in 4 minutes: 2.1 min