Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[C:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])(O)[CH2:17][CH2:18][CH2:19][CH2:20][C:14]=3[N:13]=[C:12]2[CH:28]([CH3:30])[CH3:29])=[CH:6][CH:5]=1>C(#N)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][N:11]2[C:15]3[CH:16]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:18][CH2:19][CH2:20][C:14]=3[N:13]=[C:12]2[CH:28]([CH3:29])[CH3:30])=[CH:8][CH:9]=1
Reactant: CCOC(=O)CC1(O)CCCCc2nc(C(C)C)n(Cc3ccc(Cl)cc3)c21
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: CCOC(=O)CC1CCCCc2nc(C(C)C)n(Cc3ccc(Cl)cc3)c21
Temperature: -6 °C
Yield: 14.6 %

Procedure:
A mixture of TMSCI (0.846 mL) and sodium iodide (992 mg) in acetonitrile (12 ml) was added dropwise to a stirred suspension of Intermediate 4 (670 mg) in acetonitrile, cooled to −6° C. and keeping the temperature under 0° C. The RM was stirred at −6° C. and gradually warmed up to room temp overnight. The reaction mixture was partitioned between EtOAc (50 ml) and sat NaHCO3 aq. sol.: water (1:1, 50 ml). The two phases were separated and the aqueous phase was extracted again with EtOAc (50 ml). The phases were separated; the organic extracts were combined, dried (hydrophobic frit) and concentrated under vacuum. The residue was purified on silica using a cyclohexane:ethyl acetate 0-100% gradient. The desired fractions were combined and concentrated under vacuum to give the title compound (94 mg). LC/MS MH+ 389, Rt 1.32 min (2 minute run).
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]C=C)[C@H:15]([C:36]([NH:38][C@:39]3([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:41][C@H:40]3[CH:42]=[CH2:43])=[O:37])[CH2:14]2)=[CH:4][C:3]=1[O:49][CH3:50]>ClCCl>[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]3[C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH:43]=[CH:42][C@@H:40]4[CH2:41][C@@:39]4([C:44]([O:46][CH2:47][CH3:48])=[O:45])[NH:38][C:36](=[O:37])[C@@H:15]3[CH2:14]2)=[CH:4][C:3]=1[O:49][CH3:50]
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)N[C@]1(C(=O)OCC)C[C@H]1C=C
Agent: CCOC(=O)[C@@]12C[C@H]1/C=C\CCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc3nccc4cc(OC)c(Br)cc34)C[C@H]1C(=O)N2
Solvent: ClCCl
Product: CCOC(=O)[C@@]12C[C@H]1C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](Oc3nccc4cc(OC)c(Br)cc34)C[C@H]1C(=O)N2

Procedure:
A solution of the product from Step 3 (200 mg, 0.264 mmol) in dichloromethane (26 mL) was bubbled with nitrogen gas for 30 minutes. Zhan catalyst 1B (19.4 mg, 0.026 mmol) was added, and the reaction mixture was heated at reflux under nitrogen for 2 hours. The mixture was concentrated and chromatographed on silica gel 60, eluting with 5% to 75% EtOAc in hexane to give the title product (135 mg). LRMS (ESI) m/z 729.3 [(M+H)+; calcd for C35H46BrN4O8: 729.3].
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:14]([N:18]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([OH:27])[CH:24]=2)[C:19]1=[O:28])[CH2:15][CH2:16][CH3:17].C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1CCCC1=O.[Cu]I.C(OCC)(=O)C.O>[CH2:14]([N:18]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:27][C:2]3[CH:3]=[N:4][CH:5]=[CH:6][C:7]=3[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:24]=2)[C:19]1=[O:28])[CH2:15][CH2:16][CH3:17]
Reactant: CCCCN1Cc2cc(O)ccc2C1=O
Reactant: Brc1cnccc1-c1ccccc1
Agent: [Cu]I
Agent: CC(C)(C)C(=O)CC(=O)C(C)(C)C
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Solvent: O
Product: CCCCN1Cc2cc(Oc3cnccc3-c3ccccc3)ccc2C1=O
Temperature: 220 °C
Yield: 21 %

Procedure:
A mixture of 3-bromo-4-phenylpyridine (50 mg, 0.213 mmol), 2-butyl-5-hydroxy-isoindolin-1-one (88 mg, 0.427 mmol), Cs2CO3 (139 mg, 0.427 mmol), CuI (16.3 mg, 0.085 mmol) and 2,2,6,6-tetramethyl-3.5-heptanedione (53 μL, 0.256 mmol) in degassed N-methylpyrrolidone (NMP) (2 mL) was stirred and heated in the microwave (220° C., 300 W, 30 min). Two of those reactions were combined, excess water and ethyl acetate were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were extracted with aqueous HCl (2 M) and the combined extracts were basified with aqueous NaOH (2 M) followed by extraction with ethyl acetate. The combined organic layers were washed with water and dried over MgSO4. Purification by HPLC provided 2-butyl-5-(4-phenylpyridin-3-yloxy)isoindolin-1-one (16 mg, 8%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-].[K+].[C:11](=S)=[S:12]>O>[SH:12][C:11]1[NH:8][C:7]2[C:2]([N:1]=1)=[N:3][CH:4]=[CH:5][CH:6]=2
Reactant: S=C=S
Reactant: Nc1cccnc1N
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Sc1nc2ncccc2[nH]1
Yield: 55 %

Procedure:
To 25.25 g (0.23 m) of 2,3-diaminopyridine in water is added an aqueous solution of 31.9 g (0.57 m) KOH, followed by 35 g (0.46 m) carbon disulfide. The mixture is heated to reflux for 5 hours, after which the hot mixture is filtered and the filtrate cooled. The cold solution is acidified with acetic acid and the solid is collected, washed with water and air-dried. The crude material is recrystallized in ethanol (3500 ml) with carbon. The recrystallized material weighs 19 g (55% yield).
Reaction SMILES: [F:1][C:2]([F:23])([C:19]([F:22])([F:21])[F:20])[CH2:3][CH2:4][CH2:5][CH:6]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=[CH2:18])[C:7]([O:9][CH2:10][CH3:11])=[O:8].ICCCC(F)(F)C(F)(F)F.C(OCC)(=O)CC(OCC)=O.ICCCCCC=C.[CH3:54][O:55][C:56]1[CH:65]=[C:64]2[C:59]([C@H:60]([CH2:75]C=C)[C@@:61]([C:67]3[CH:72]=[CH:71][C:70]([O:73][CH3:74])=[CH:69][CH:68]=3)([CH3:66])[CH2:62][S:63]2)=[CH:58][CH:57]=1>ClCCl.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1C=CC(C=[Ru](Cl)Cl)=CC=1>[CH3:54][O:55][C:56]1[CH:65]=[C:64]2[C:59]([C@H:60]([CH2:75][CH:18]=[CH:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH:6]([CH2:5][CH2:4][CH2:3][C:2]([F:23])([F:1])[C:19]([F:20])([F:21])[F:22])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[C@@:61]([C:67]3[CH:68]=[CH:69][C:70]([O:73][CH3:74])=[CH:71][CH:72]=3)([CH3:66])[CH2:62][S:63]2)=[CH:58][CH:57]=1
Reactant: C=CC[C@H]1c2ccc(OC)cc2SC[C@@]1(C)c1ccc(OC)cc1
Reactant: C=CCCCCCC(CCCC(F)(F)C(F)(F)F)C(=O)OCC
Agent: Cl[Ru](Cl)=Cc1ccccc1
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: C=CCCCCCI
Solvent: ClCCl
Solvent: CCOC(=O)CC(=O)OCC
Product: CCOC(=O)C(CCCCCC=CC[C@H]1c2ccc(OC)cc2SC[C@@]1(C)c1ccc(OC)cc1)CCCC(F)(F)C(F)(F)F
Yield: 72 %

Procedure:
Ethyl 2-(4,4,5,5,5-pentafluoropentyl)-8-nonenoate was separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-6-heptene. A solution of this compound (4.55 g, 13.21 mmol), (3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman (2.5 g, 7.342 mmol) and benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (302 mg, 0.367 mmol) in dichloromethane (60 ml) was heated under reflux for 6 hours. After the reaction was completed, the solvent was distilled off and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30) to give ethyl 10-[(3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)-8-decenoate (3.46 g, Yield 72%) as an oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:11](=[O:28])[NH:10]2)=[C:5]([N+:29]([O-:31])=[O:30])[CH:4]=1)#[N:2].[CH3:32][Si](C)(C)[N-][Si](C)(C)C.[Li+].IC>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C:14]([C:15]#[N:16])=[C:13]([CH3:17])[N:12]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:26])([F:27])[F:25])[CH:19]=3)[C:11](=[O:28])[N:10]2[CH3:32])=[C:5]([N+:29]([O-:31])=[O:30])[CH:4]=1)#[N:2]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2[N+](=O)[O-])NC(=O)N1c1cccc(C(F)(F)F)c1
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Product: CC1=C(C#N)[C@@H](c2ccc(C#N)cc2[N+](=O)[O-])N(C)C(=O)N1c1cccc(C(F)(F)F)c1
Reaction time: 0.5 h

Procedure:
The reaction was carried out under argon. (4R)-4-(4-Cyano-2-nitrophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (5.0 g, 11.7 mmol) was initially charged in absolute THF (500 ml), and a 1 M solution of lithium hexamethyldisilazide (LiHMDS) in THF (13.5 ml, 13.5 mmol, 1.15 eq.) was added at −78° C. After 30 min of stirring, iodomethane (8.30 g, 58.5 mmol; 5 eq.) in THF was added, and the mixture was stirred with gradual warming from −78° C. to RT for 16 h. The reaction mixture was then concentrated under reduced pressure, and initially 1N hydrochloric acid (14.0 ml), and then MTBE (500 ml) were added. The organic phase was washed successively with water (2×), saturated sodium bicarbonate solution, saturated ammonium chloride solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The title compound was obtained as a solid (4.3 g, 83% of theory).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C:19]1[C:28](Br)=[N:27][C:26]([Br:30])=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22].C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:18][C:19]1[C:28]([C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)=[N:27][C:26]([Br:30])=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22]
Reactant: OB(O)c1ccc(OCc2ccccc2)cc1
Reactant: COC(=O)c1cc(Br)nc(Br)c1N
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: COC(=O)c1cc(Br)nc(-c2ccc(OCc3ccccc3)cc2)c1N
Yield: 61.6 %

Procedure:
A mixture of 4-(benzyloxy)phenylboronic acid (3.53 g, 15.5 mmol), methyl 3-amino-2,6-dibromoisonicotinate (4.0 g, 12.9 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.90 g, 0.77 mmol), sodium carbonate (3.28 g, 31.0 mmol) was flushed with nitrogen and toluene (32 mL), and MeOH (11 mL) were added. The reaction was heated at reflux under nitrogen for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate and the solvent removed. Radial chromatography (step gradient elution with hexane containing 20 to 80% DCM) afforded methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (3.28 g, 7.94 mmol, 62% yield) as a yellow solid. MS (ESI) m/z 415.0 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (1H, s), 7.52-7.58 (2H, m), 7.41-7.46 (2H, m), 7.36-7.41 (2H, m), 7.30-7.36 (1H, m), 7.04-7.09 (2H, m), 5.95 (2H, br. s.), 3.92 (3H, s).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][C@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:12]=[CH:13][C:14]3[S:19][CH2:18][C:17](=[O:20])[NH:16][C:15]=3[CH:21]=2)[CH2:6]1.[Cl:22][C:23]1[C:28]2[NH:29]C(=O)[O:31][C:32](=O)[C:27]=2[CH:26]=[CH:25][CH:24]=1>>[NH2:29][C:28]1[C:23]([Cl:22])=[CH:24][CH:25]=[CH:26][C:27]=1[C:32]([NH:1][CH2:2][CH2:3][CH2:4][C@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:12]=[CH:13][C:14]3[S:19][CH2:18][C:17](=[O:20])[NH:16][C:15]=3[CH:21]=2)[CH2:6]1)=[O:31]
Reactant: O=c1[nH]c2c(Cl)cccc2c(=O)o1
Reactant: NCCC[C@@H]1CN(c2ccc3c(c2)NC(=O)CS3)C(=O)O1
Product: Nc1c(Cl)cccc1C(=O)NCCC[C@@H]1CN(c2ccc3c(c2)NC(=O)CS3)C(=O)O1
Yield: 70 %

Procedure:
Starting from 6-[(R)-5-(3-amino-propyl)-2-oxo-oxazolidin-3-yl]-4H-benzo[1,4]thiazin-3-one (described in WO 2010/041219) and 8-chloro-1H-benzo[d][1,3]oxazine-2,4-dione and using Procedure A, the title compound was obtained as a colourless solid (97 mg; 70% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:15]([CH:16]=1)=[C:14]1[C:9]([CH:10]=[CH:11][CH:12]=[CH:13]1)=[N:8][C:7]=2[CH3:17].[BH4-].[Na+].FC(F)(F)C(O)=O.C1C=CC2C3C=CC=CC=3NCC=2C=1.C(N(CC)CC)C.[CH3:48][O:49][C:50]1[CH:55]=[CH:54][C:53]([S:56](Cl)(=[O:58])=[O:57])=[CH:52][C:51]=1[CH3:60]>O1CCCC1.ClCCl>[CH:4]1[CH:3]=[CH:16][C:15]2[C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[NH:8][CH2:7][C:6]=2[CH:5]=1.[CH3:1][O:2][C:3]1[CH:16]=[C:15]2[C:6]([CH:7]([CH3:17])[N:8]([S:56]([C:53]3[CH:54]=[CH:55][C:50]([O:49][CH3:48])=[C:51]([CH3:60])[CH:52]=3)(=[O:58])=[O:57])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=32)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(C)nc3ccccc3c2c1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1C
Agent: [BH4-]
Agent: [Na+]
Agent: c1ccc2c(c1)CNc1ccccc1-2
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Product: COc1ccc2c(c1)-c1ccccc1N(S(=O)(=O)c1ccc(OC)c(C)c1)C2C

Procedure:
The intermediate dihydrophenanthridine was prepared from 9-methoxy-6-methylphenanthridine, (Example 36, Step b, 0.7 g, 3.1 mmol), by treatment with sodium borohydride (0.48 g, 12.6 mmol) and trifluoroacetic acid (0.5 mL, 6.3 mmol) in tetrahydrofuran (35 mL). In a separate, second step, the dihydrophenanthridine was treated with triethylamine (1.1 mL, 7.9 mmol) and 4-methoxy-3-methylbenzenesulfonyl chloride (0.87 g, 3.9 mmol, 2 equivalents) in dichloromethane (10 mL) according to the procedure and in the same manner as described in Example 32, Method A, Step d. The crude product was purified by flash column chromatography on silica gel, eluting with a mixture of ethyl acetate-hexane (1:9 to 3:7 gradient), to yield 9-methoxy-5-[(4-methoxy-3-methylphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine as a homogeneous, white solid (0.27 g, 33% from the dihydrophenanthridine);
Reaction SMILES: CS([C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[Br:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24][NH2:25]>>[Br:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][CH:28]=1)[CH2:24][NH:25][C:5]1[N:10]=[C:9]([N:11]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[N:13]=[CH:12]2)[CH:8]=[CH:7][N:6]=1
Reactant: CS(=O)(=O)c1nccc(-n2cnc3ccccc32)n1
Reactant: NCc1cccc(Br)c1
Product: Brc1cccc(CNc2nccc(-n3cnc4ccccc43)n2)c1

Procedure:
2-Methanesulfonyl-4-[benzimidazol-1-yl]pyrimidine was reacted with 3-bromobenzylamine according to the procedure described in EXAMPLE 1, Step C to afford the title compound. Mass Spectrum (ESI): m/e 380.2, 382.2 (M+1). 1H NMR (500 MHz, CDCl3): δ partial 8.58 (s, 1H); 8.44 (d, J=5.3 Hz, 1H); 8.01 (br s, 1H); 7.85 (m, 1H); 7.58 (s, 1H); 7.45 (d, J=7.5 Hz, 1H); 6.87 (d, J=5.5 Hz, 1H); 5.83 (br s, 1H); 4.74 (d, J=6.1 Hz, 2H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:19])[C:9]2[CH:17]=[C:16]3[C:12]([C:13]([CH3:18])=[N:14][NH:15]3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30]Br>CN(C=O)C.C(OCC)(=O)C>[Cl:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][N:14]1[C:13]([CH3:18])=[C:12]2[C:16]([CH:17]=[C:9]([N:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)[CH3:19])[CH:10]=[CH:11]2)=[N:15]1
Reactant: Cc1n[nH]c2cc(N(C)c3ccnc(Cl)n3)ccc12
Reactant: Clc1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1c2ccc(N(C)c3ccnc(Cl)n3)cc2nn1Cc1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-(2-chloropyrimidin-4-yl)-N,3-dimethyl-1H-indazol-6-amine (2 g, 7.31 mmol) was dissolved in DMF (15 ml), and Cs2CO3 (2 g, 14.6 mmol) and 3-chlorobenzyl bromide (1.25 ml, 9.5 mmol) were added at room temperature. Mixture was stirred at rt for overnight. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated. The aqueous layer was thoroughly extracted with EtOAc. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated to give 2-(3-chlorobenzyl)-N-(2-chloropyrimidin-4-yl)-N,3-dimethyl-2H-indazol-6-amine as an off-white solid . 1H NMR (300 MHz, d6DMSO) δ 7.94 (d, J=6.0 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.56 (d, J=1.3 Hz, 1H), 7.36-7.38 (m, 2H), 7.32 (br s, 1H), 7.16 (m, 1H), 6.91 (m, 1H), 6.28 (d, J=6.1 Hz, 1H), 5.65 (s, 2H), 3.42 (s, 3H), 2.63 (s, 3H). MS (ES+, m/z) 398 (M+H).
Reaction SMILES: CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:24]=[C:23]2[C:11]([CH2:12][C:13]3[CH:17]=[C:16]([CH3:18])[N:15]([CH2:19][CH:20](O)[CH3:21])[C:14]=32)=[CH:10][CH:9]=1.C(N(CC)CC)C.[N-:32]=[N+:33]=[N-:34].[Na+]>ClCCl.CN(C)C=O.O>[N:32]([CH:20]([CH3:21])[CH2:19][N:15]1[C:16]([CH3:18])=[CH:17][C:13]2[CH2:12][C:11]3[C:23]([C:14]1=2)=[CH:24][C:8]([O:7][CH3:6])=[CH:9][CH:10]=3)=[N+:33]=[N-:34]
Reactant: COc1ccc2c(c1)-c1c(cc(C)n1CC(C)O)C2
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2c(c1)-c1c(cc(C)n1CC(C)N=[N+]=[N-])C2
Yield: 62.8 %

Procedure:
0.81 ml of methanesulfonyl chloride was added dropwise while stirring to a solution, cooled to 0°, of 1.35 g of (RS)-1-(7-methoxy-2-methyl-1,4-dihydro-indeno[1,2-b]pyrrol-1-yl)-propan-2-ol and 2.92 ml of triethylamine in 60 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 120 ml of dichloromethane, washed twice with 70 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 70 ml of dichloromethane. The combined organic phases were washed with 90 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 40 ml of anhydrous dimethylformamide, treated with 0.68 g of sodium azide and the reaction mixture was heated to 80° for 23 hours while stirring. After cooling, the solution was poured into 70 ml of water and extracted twice with 100 ml of ethyl acetate each time. The combined organic phases were washed once with 70 ml of water and once with 70 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (toluene). 0.93 g (63%) of (RS)-1-(2-azido-propyl)-7-methoxy-2-methyl-1,4-dihydro-indeno[1,2-b]pyrrole was obtained as a light yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]([OH:16])=[O:15])[CH:13]=1)[N:10]=[CH:9][NH:8][C:7]2=[O:17])([O-:3])=[O:2].S(=O)(=O)(O)O.[OH-].[Na+].[CH3:25]O>>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]([O:16][CH3:25])=[O:15])[CH:13]=1)[N:10]=[CH:9][NH:8][C:7]2=[O:17])([O-:3])=[O:2]
Reactant: O=C(O)c1cc([N+](=O)[O-])cc2c(=O)[nH]cnc12
Reactant: CO
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: COC(=O)c1cc([N+](=O)[O-])cc2c(=O)[nH]cnc12
Temperature: 25 °C
Yield: 84 %

Procedure:
6-nitro-4-oxo-3,4-dihydroquinazoline-8-carboxylic acid (500 mg, 2.13 mmol) was treated with a solution of sulfuric acid ((1.2 equiv.) in anhydrous MeOH (10 mL) under refluxing overnight. After cooling to rt, 2N NaOH solution was added to the reaction mixture to adjust pH˜8. After removal of MeOH, methyl ester was collected by filtration, and washing with water and as yellow solid in 84% yield. 1HNMR (in DMSO): 3.91 (s, 3H), 8.38 (s, 1H), 8.74 (d, J=2.6 Hz, 1H), 8.88 (d, J=2.6 Hz, 1H). Mass: M+H+: 250.
Reaction SMILES: [N:1]([CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1)=[O:6])=[N+:2]=[N-:3].B.C1COCC1>C1COCC1>[N:1]([CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1)[OH:6])=[N+:2]=[N-:3]
Reactant: CSc1ccc(C(=O)CN=[N+]=[N-])cc1
Agent: B
Solvent: C1CCOC1
Product: CSc1ccc(C(O)CN=[N+]=[N-])cc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 102 %

Procedure:
A solution consisting of 2-azido-1-(4-methylsulfanyl-phenyl)-ethanone (1.69 g, 8.15 mmol) and THF (8.15 mL) was cooled to 0° C. before slowly adding BH3.THF (1.0 M solution, 8.15 ml) over 10 min. The resulting solution was stirred at 0° C. for 2 h. The reaction was quenched by slow addition of MeOH (10 mL) at 0° C., and then concentrating to dryness to yield the title compound (1.74 g, 100%).
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@H:9]2[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@H:12]([OH:17])[O:11][C@@H:10]2[CH2:18][OH:19])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.[H][H]>[Ni]>[CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@@H:9]([C@H:14]([OH:15])[C@@H:13]([OH:16])[CH2:12][OH:17])[C@H:10]([OH:11])[CH2:18][OH:19])[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22]
Reactant: [H][H]
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: [Ni]
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: OC[C@@H](O)[C@@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)[C@@H](O)CO

Procedure:
A commercially available aqueous solution of high purity maltose (mfd. by NIHON SHOKUHIN KAKO K.K., concentration: 60%, sugar composition in the solid component: maltose: 81.6%, glucose: 1.5%, sugar of equal or more than DP3: 16.9%) was reduced under the existence of Raney nickel catalyst at a hydrogen pressure of 100 kg/cm2 and 130° C. for 120 minutes, to obtain aqueous solution of maltitol.
Reaction SMILES: C([Li])CCC.[CH2:6]([O:8][C:9]1[CH:17]=[CH:16][C:15]2[N:14]3[CH2:18][CH2:19][CH2:20][C:13]3=[C:12](I)[C:11]=2[CH:10]=1)[CH3:7].[C:22]([O:26][C:27]([N:29]1[C@@H:33]([CH3:34])[CH2:32]OS1(=O)=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCCCCC.O1CCCC1>[C:22]([O:26][C:27](=[O:28])[NH:29][CH:33]([CH3:32])[CH2:34][C:12]1[C:11]2[CH:10]=[C:9]([O:8][CH2:6][CH3:7])[CH:17]=[CH:16][C:15]=2[N:14]2[CH2:18][CH2:19][CH2:20][C:13]=12)([CH3:25])([CH3:24])[CH3:23]
Reactant: CCOc1ccc2c(c1)c(I)c1n2CCC1
Reactant: C[C@H]1COS(=O)(=O)N1C(=O)OC(C)(C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOc1ccc2c(c1)c(CC(C)NC(=O)OC(C)(C)C)c1n2CCC1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 61.4 %

Procedure:
75 mL of a pre-cooled (−78° C.) 1.6M solution of n-butyllithium in n-hexane at −78° C. was added over 30 min to a suspension of 32.72 g (0.100 mol) 6-ethoxy-8-iodo-2,3-dihydro-1H-3a-aza-cyclopenta[a]indene in 330 mL dry tetrahydrofuran. The mixture was stirred 5 min at −78° C. and 30.85 g (S)-4-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester was added in one portion. The mixture was stirred 20 min at −78° C. The reaction mixture was allowed to warm to −30° C. over 50 min. To the resulting slightly turbid mixture was added 300 mL of 10% citric acid. The phases were separated and the aqueous phase was extracted with 200 mL hexane. The combined organic phases were washed with 200 mL brine, dried over magnesium sulfate and evaporated. The residue was taken up in 200 mL dichloromethane and purified by chromatography on 1500 g silica gel (43-60 mesh) with dichloromethane (4000 mL) and 19:1 dichloromethane/ethyl acetate (6000 mL). The product fractions were evaporated and the residue was dissolved in 200 mL dichloromethane. The solution was diluted with 1000 mL hexane and the mixture was concentrated to a volume of 800 mL. The resulting suspension was stirred 18 h at room temperature. The mixture was cooled to 0° C. and stirred 30 min. The product was collected by filtration to yield 22.00 g of the title compound. The mother liquor was purified by chromatography, resulting in a further 4.71 g of the title compound. Total yield: 26.71 g (74.5%). m.p.: 89-90° C.