Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([OH:4])[CH3:3].C(N(CC)CC)C.[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19](F)=[O:20])=[N:17][CH:18]=1>O>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([O:4][CH:2]([CH3:3])[CH3:1])=[O:20])=[N:17][CH:18]=1
Reactant: CC(C)O
Reactant: O=C(F)c1ccc(F)cn1
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)OC(=O)c1ccc(F)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 23 %

Procedure:
Anhydrous 2-propanol (0.361 g, 6 mmol) and anhydrous tri-ethylamine (0.405 g, 4 mmol) were added drop-wise at room temperature to the 5-fluoropicolinoyl fluoride provided above. The mixture was stirred at room temperature overnight, poured into a reparatory funnel with water and extracted with ethyl ether. The organic phase was then washed with water and dried over MgSO4. The solvent was removed with a rotary evaporator. The concentrated crude product was purified using column chromatography (silica gel) with ethyl acetate/hexanes mixture (1/10) as eluent to give 0.17 g (23% yield, 96% LC purity) of desired product as an off-white solid. GC/MS results were consistent with the chemical formula of isopropyl 5-fluoropicolinate: 70 eV EIMS (GC) m/z=142 (43%), 124 (100%), 97 (97%), 96 (93%), 43 (59%). 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J=2.8 Hz, 1H), 8.18 (dd, J=8.8, 4.4 Hz, 1H), 7.52 (ddd, J=8.7, 7.9, 2.9 Hz, 1H), 5.34 (hept, J=6.3 Hz, 1H), 1.43 (d, J=6.3 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 163.63 (s), 162.32 (s), 159.71 (s), 144.84 (d, J=3.8 Hz), 138.46 (d, J=24.8 Hz), 126.78 (d, J=5.4 Hz), 123.31 (d, J=18.5 Hz), 69.71 (s), 21.81 (s). 19F NMR (376 MHz, CDCl3) δ −120.51.
Reaction SMILES: [Cl-:1].[Cl-].[Cl-].[CH:4]1([Zr+3:13])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5]1.[CH3:14][C-:15]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16]1.[Li+]>CCOCC>[Cl-:1].[Cl-:1].[CH3:20][C:17]1([Zr+2:13][CH:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:6]=[CH:5]2)[CH:18]=[CH:19][C:15]([CH3:14])=[CH:16]1
Reactant: Cc1cc[c-](C)c1
Reactant: [Zr+3]C1C=Cc2ccccc21
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOCC
Product: CC1=CC(C)([Zr+2]C2C=Cc3ccccc32)C=C1
Reaction time: 17 h

Procedure:
To a yellow-orange suspension of indenylzirconium trichloride, IndZrCl3, (1.00 g, 3.20 mmol, 1.00 equiv.) in ether (30 mL) was added lithium 1,3-dimethylcyclopentadienide (0.32 g, 3.20 mmol, 1.00 equiv.). The reaction quickly turned yellow with much precipitate. The reaction was stirred 17 hours and then evaporated in vacuo, leaving yellow solid. The solid was extracted with dichloromethane (20 mL, then 2×10 mL) and the extracts were filtered to give yellow solid and a yellow solution. The solution was evaporated in vacuo, leaving bright yellow solid. Yield 1.07 g (90%). 1H NMR(CD2Cl2): δ 2.09 (s, 3H, Me), 5.65 (d, 2H), 5.94 (t, 1H), 6.48 (d, 2H), 6.82 (t, 1H), 7.28 (m, 2H, Ind), 7.64 (m, 2H, Ind).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[N:9][N:10]([CH2:18][C:19](OCC)=[O:20])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>>[C:1]1([C:7]2[CH:8]=[N:9][N:10]([CH2:18][C:19]([NH:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:20])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)Cn1ncc(-c2ccccc2)c1-c1ccccc1
Reactant: NCCCN1CCCC1
Product: O=C(Cn1ncc(-c2ccccc2)c1-c1ccccc1)NCCCN1CCCC1
Temperature: 100 °C
Reaction time: 48 h

Procedure:
A mixture of 15 g (0.049 mol) of ethyl 4,5-diphenyl-1H-pyrazole-1-acetate and 60 mL of N-(3-aminopropyl) pyrrolidine was stirred at 100° C. for 48 hr. The excess aminopropylpyrrolidine was stripped in vacuo and the residue was triturated in ether to yield 5.5 g of product mp 75°-79° C.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH3:29])[N:23]=3)=[CH:20][CH:19]=[CH:18][N:17]=2)=[C:11]([CH3:30])[CH:10]=1)=[O:7])=O.[CH3:34][N:35]([CH3:39])[CH2:36][CH2:37][NH2:38].CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[CH3:34][N:35]([CH3:39])[CH2:36][CH2:37][NH:38][CH2:1][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[C:21]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH:28][CH3:29])[N:23]=3)=[CH:20][CH:19]=[CH:18][N:17]=2)=[C:11]([CH3:30])[CH:10]=1)=[O:7]
Reactant: CNc1nccc(-c2cccnc2Oc2ccc(NC(=O)c3cccc(C=O)c3)cc2C)n1
Reactant: CN(C)CCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CNc1nccc(-c2cccnc2Oc2ccc(NC(=O)c3cccc(CNCCN(C)C)c3)cc2C)n1
Reaction time: 16 h

Procedure:
To 3-formyl-N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide (0.100 g, 0.23 mmol) in MeOH (6 mL) was added N1,N1-dimethylethane-1,2-diamine (0.13 mL, 1.1 mmol) and AcOH (0.010 mL, 0.23 mmol). The reaction was allowed to stir for 2.5 h, at which point sodium triacetoxyborohydride (0.096 g, 0.46 mmol) was added. After approximately 16 h, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate. The aqueous layer was extracted four times with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give a solid. Purification by reverse-phase HPLC using acetonitrile/water/TFA as eluent gave 3-((2-(dimethylamino)ethylamino)methyl)-N-(3-methyl-4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide as a white solid. MS m/z=512 [M+1]+. Calc'd for C29H33N7O2: 511.63.
Reaction SMILES: CN(C)[N:3]=[CH:4][C:5](=[CH2:7])[CH3:6].[C:9]1([C:15]2[C:16](=[O:29])[NH:17][C:18]3[C:23]([CH:24]=2)=[C:22]([O:25]C)[CH:21]=[CH:20][C:19]=3[O:27]C)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)(Cl)Cl>[CH3:6][C:5]1[CH:7]=[C:21]2[C:20](=[N:3][CH:4]=1)[C:19](=[O:27])[C:18]1[NH:17][C:16](=[O:29])[C:15]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)=[CH:24][C:23]=1[C:22]2=[O:25]
Reactant: COc1ccc(OC)c2[nH]c(=O)c(-c3ccccc3)cc12
Reactant: C=C(C)C=NN(C)C
Solvent: ClC(Cl)Cl
Product: Cc1cnc2c(c1)C(=O)c1cc(-c3ccccc3)c(=O)[nH]c1C2=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 53.4 %

Procedure:
Methacrolein dimethylhydrazone (90 mg, 0.75 mmol) in one portion was added to a solution of 3-phenyl-5,8-dimethoxy-2-(1H)-quinolinone (190 mg, 0.71 mmol) in chloroform (50 ml.) The solution was agitated at room temperature for 3 hours and was evaporated. The residue was chromatographed over silica gel, eluting with ethyl acetate to give 120 mg (50%) of 6-methyl-3-phenyl-1H-1,8-diazaanthracen-2,9,10-trione (I-j). m.p. 275° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[CH:10][N:9]=2)[CH:3]=1.Cl.[CH2:18]([NH2:21])[C:19]#[CH:20].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2[CH:13]=[C:12]([C:14]([NH:21][CH2:18][C:19]#[CH:20])=[O:16])[CH:11]=[CH:10][N:9]=2)[CH:3]=1
Reactant: Cc1ccnc(-c2cc(C(=O)O)ccn2)c1
Reactant: C#CCN
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C#CCNC(=O)c1ccnc(-c2cc(C)ccn2)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
4′-Methyl-2,2′-bipyridine-4-carboxylic acid (0.22 g, 1 mmol), propargylamine hydrochloride (0.092 g, 1 mmol), HOBt (0.15 g, 1 mmol) and DIPEA (0.21 ml) were dissolved in dry DMF (15 ml) and cooled to 0° C. DCC (0.25 g, 1.2 mmol) was dissolved in DMF (3 ml) and added dropwise to the reaction mixture. The mixture was stirred at room temperature overnight. DCU was filtered off and solvent was removed by vacuum distillation. The remaining solid compound was dissolved in ethyl acetate and washed with NaHCO3(5%), 0.5 N HCl, brine and dried over sodium sulfate. Solvent was removed by rotary evaporator and the compound was purified by column chromatography using 2% methanol in chloroform as eluent afforded 0. 19 g (76%). FAB-MS: M.W. 251 [M+]; NMR assigned.
Reaction SMILES: [CH3:1][Si]([N-][Si](C)(C)C)(C)C.[K+].[Br-].[F:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[C:22](=O)[CH3:23]>C1(C)C=CC=CC=1.C1COCC1>[F:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][C:14]=1[C:22]([CH3:23])=[CH2:1]
Reactant: CC(=O)c1cc([N+](=O)[O-])ccc1F
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: C=C(C)c1cc([N+](=O)[O-])ccc1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
KHMDS (1 eq) in toluene is added dropwise over 5 minutes to a stirred suspension of triphenylphosphinemethyl bromide (1.2 eq) in THF at −78° C. under nitrogen. After complete addition solution is allowed to warm to room temperature for 5 minutes then cooled a second time to 78° C. 1-(2-fluoro-5-nitrophenyl)ethanone (1 eq) in THF is then added via cannulla into the cold suspension over 10 minutes. Resulting mixture is then allowed to warm to room temperature and stirred for 1 h. Solvent is then removed under reduced pressure, cyclohexane is then added and mixture heated briefly to reflux, cooled to room temperature, filtered and filtrate concentrated. Crude product is purified using flash chromatography (85% Hex:15% EtoAc) on silica to afford 1-fluoro-4-nitro-2-(prop-1-en-2-yl)benzene.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[Li]CCCC.[C:17]1(=[O:26])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][CH2:18]1.Cl>C1COCC1>[N:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[C:17]2([OH:26])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][CH2:18]2)[CH:7]=[CH:8][CH:9]=1
Reactant: Brc1cccc2cccnc12
Reactant: O=C1CCc2ccccc21
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OC1(c2cccc3cccnc23)CCc2ccccc21
Temperature: -100 °C
Reaction time: 0.25 h

Procedure:
8-Bromoquinoline (10.4 g, 50 mmol) was introduced into 100 ml of THF, and the mixture was cooled to about −100° C. 20 ml of n-BuLi (2.5 M in hexane, 50 mmol) were added dropwise, during which the internal temperature was kept below −80° C. When the addition was complete, the mixture was stirred at −80° C. for a further 15 minutes, and 6.6 g of 1-indanone (50 mmol), dissolved in 30 ml of THF, were then added dropwise. The reaction mixture was then allowed to warm slowly to room temperature, and was then refluxed for 3 hours. After the mixture had cooled to room temperature, firstly ice and then hydrochloric acid were added to about pH 1, and the mixture was stirred for 30 minutes. The aqueous and organic phases were separated, the aqueous phase was treated with ammonia solution to about pH 9 and extracted with ether, and the combined organic phases were subsequently evaporated to dryness under reduced pressure. The viscous oil obtained in this way (1-(8-quinolyl)-indan-1-ol (8H2O)) was treated with hydrochloric acid to pH 0, refluxed for 2 hours and subsequently neutralized. After work-up and drying, 6.6 g of 1-(8-quinolyl)indene (55%) were isolated as a colorless solid.
Reaction SMILES: [O:1]1[CH2:3][C@@H:2]1[C@@H:4]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C@@H:23]1([NH2:33])[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)CCC1.[CH2:34]([OH:36])C>>[CH2:5]([C@H:4]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@H:2]([OH:1])[CH2:3][NH:33][CH2:23][C:32]1[CH:31]=[CH:30][CH:29]=[C:28]([O:36][CH3:34])[CH:27]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCO
Reactant: N[C@H]1CCCc2ccccc21
Reactant: O=C(N[C@@H](Cc1ccccc1)[C@H]1CO1)OCc1ccccc1
Product: COc1cccc(CNC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)OCc2ccccc2)c1

Procedure:
A mixture of benzyl (1S)-1-[(2S)-oxiranyl]-2-phenylethylcarbamate (V, 0.22 g, 0.74 mmol), 3-methoxybenzylamine (VI, 0.13 g, 0.92 mmol), and ethanol (2 mL) is stirred at reflux for 2.3 hours and then cooled and concentrated under reduced pressure. The residue is chouromatographed (silica gel; methanol/dichloromethane/ammonium hydroxide, 4/96/trace) to give the title compound, MS m/z at (m+H)+=435.2.
Reaction SMILES: [H-].[Na+].P(=O)([O-])O[C:5]([CH2:14][CH3:15])(CC)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.P(=O)([O-])[O-].[CH3:22][C:23]1[N:24]=C(C=O)[S:26][CH:27]=1>COCCOC.C(OCC)(=O)C>[CH3:22][C:23]1[N:24]=[C:15]([CH:14]=[CH:5][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[S:26][CH:27]=1
Reactant: CCC(CC)(O[PH](=O)[O-])c1ccccc1
Reactant: Cc1csc(C=O)n1
Agent: O=[PH]([O-])[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: Cc1csc(C=Cc2ccccc2)n1
Temperature: 0 °C
Reaction time: 4 h
Yield: 15.9 %

Procedure:
Sodium hydride (102 mg of a 60% suspension in mineral oil, 4.3 mmol) was slurried in dry 1,2-dimethoxyethane (DME) under argon, cooled to 0° C. in an ice bath, and diethylbenzyl phosphonate (0.89 mL, 4.3 mmol) was added dropwise to the suspension. Thirty minutes after the completion of the phosphonate addition, 4-methylthiazole-2-carboxaldehyde (120 mg, 0.94 mmol) was added as a solution in DME (5 mL). After stirring for 4 h, further NaH (40 mg of a 60% suspension in mineral oil, 1.0 mmol) was added and the reaction mixture was allowed to warm to ambient temperature and stir for 16 h. The reaction mixture was quenched by the addition of water (20 mL) and ethyl acetate (50 mL). The aqueous phase was extracted with ethyl acetate (2×30 mL), the combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 90:10 hexane:ethyl acetate to afford 4-methyl-2-[2-phenylethenyl]-1,3-thiazole (30 mg, 16% yield) as an oil. 1H NMR analysis showed the material to be a 10:1 mixture of E and Z isomers (spectral data are reported for the major isomer). 1H NMR (CDCl3,300 MHz) δ: 7.54-7.51 (m, 2H) 7.42-7.23 (m, 5H) 6.80 (s, 1H) 2.47 (s, 3H). MS (ESI) (minor isomer) 202.2 (M++H), (major isomer) 201.6 (M+).
Reaction SMILES: [Br:1][C:2]1[C:3]([C:8]([F:11])([F:10])[F:9])=[N:4][NH:5][C:6]=1[CH3:7].C([O-])([O-])=O.[K+].[K+].Cl[CH2:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH2:24][CH2:23]1)=[O:21].CN(C=O)C>CCCCCC.C(OCC)(=O)C>[F:34][C:31]1[CH:30]=[CH:29][C:28]([N:25]2[CH2:24][CH2:23][N:22]([C:20](=[O:21])[CH2:19][N:5]3[C:6]([CH3:7])=[C:2]([Br:1])[C:3]([C:8]([F:9])([F:11])[F:10])=[N:4]3)[CH2:27][CH2:26]2)=[CH:33][CH:32]=1
Reactant: O=C(CCl)N1CCN(c2ccc(F)cc2)CC1
Reactant: Cc1[nH]nc(C(F)(F)F)c1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1c(Br)c(C(F)(F)F)nn1CC(=O)N1CCN(c2ccc(F)cc2)CC1

Procedure:
Protocol T was followed using 4-Bromo-5-methyl-3-trifluoromethyl-1H-pyrazole, K2CO3, 2-Chloro-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone and DMF. Column chromatography using a solvent mixture (hexane/ethyl acetate=2/3) afforded the title compound as white solid. 1H NMR (400 MHz, CDCl3): 6.96–7 (m, 2H), 6.84–6.9 (m, 2H), 5 (s, 2H), 3.6–3.8 (m, 4H), 3.02–3.16 (m, 4H), 2.3 (s, 3H). 13C NMR (400 MHz, CDCl3): 162.6, 146.5, 142, 118.5, 116, 52.2, 50.4, 46, 42.2, 15.
Reaction SMILES: Cl.Cl.[CH2:3]([NH:10][NH2:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.O=[C:22]([CH2:28][C:29](=O)[CH3:30])[C:23]([O:25]CC)=[O:24]>CCO>[CH2:3]([N:10]1[C:29]([CH3:30])=[CH:28][C:22]([C:23]([OH:25])=[O:24])=[N:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CCOC(=O)C(=O)CC(C)=O
Reactant: NNCc1ccccc1
Agent: Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)O)nn1Cc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 92.5 %

Procedure:
To a solution of 1-benzylhydrazine dihydrochloride (Aldrich, 0.98 g, 5.0 mmol) in EtOH (30 mL) were added DIEA (2.0 mL) and ethyl 2,4-dioxopentanoate (0.70 mL, 5.0 mmol). The mixture was stirred at room temperature for 12 h and was concentrated in vacuo. The residue was dissolved in 1 N NaOH (10 mL). The solution was heated at 60° C. for 1 h. After cooling down, the solution was extracted with DCM (3×50 mL). The aqueous layer was neutralized to pH 2.0 and then was extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. It was filtered and concentrated to give 1-benzyl-5-methyl-1H-pyrazole-3-carboxylic acid (1.0 g, 92% yield). MS(ESI+): m/z 217.12 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]1[N:16]=[C:15]([C:17]3[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:40])=[O:39])=[CH:19][C:20]4[O:24][C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)=[C:22]([C:32]([NH:34][CH3:35])=[O:33])[C:21]=4[CH:36]=3)[CH:14]=[CH:13][C:12]=1[CH:43]([F:46])[CH2:44]O)[NH:6]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(Cl)Cl>[F:46][CH:43]1[CH2:44][N:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[C:2]([F:1])[C:3]=3[CH:4]=[C:5]2[C:11]2[N:16]=[C:15]([C:17]3[C:18]([N:37]([CH3:42])[S:38]([CH3:41])(=[O:39])=[O:40])=[CH:19][C:20]4[O:24][C:23]([C:25]5[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=5)=[C:22]([C:32]([NH:34][CH3:35])=[O:33])[C:21]=4[CH:36]=3)[CH:14]=[CH:13][C:12]1=2
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc(C(F)CO)c(-c4cc5c(F)cccc5[nH]4)n3)cc12
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(-c3ccc4c(n3)-c3cc5c(F)cccc5n3CC4F)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 55.3 %

Procedure:
To a solution of 5-(6-(4-fluoro-1H-indol-2-yl)-5-(1-fluoro-2-hydroxyethyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (465 mg, 0.717 mmol) and triphenylphosphine (282 mg, 1.075 mmol) in DCM (15 mL) was added diisopropyl azodicarboxylate (217 mg, 1.075 mmol). The resulting mixture was stirred at RT overnight and concentrated in vacuo. The resulting residue was purified using column chromatography (eluted with 20-50% ethyl acetate/hexane) to provide 5-(5,11-difluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (250 mg, yield: 55%). MS (M+H)+: 631.
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[CH:3]=1.I[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>[Cu].C(OCC)(=O)C>[Cl:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:4]=2[CH:3]=1
Reactant: Clc1ccc2c(c1)[nH]c1ccccc12
Reactant: Ic1ccccc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Clc1ccc2c3ccccc3n(-c3ccccc3)c2c1
Temperature: 25 °C
Yield: 57.4 %

Procedure:
Next, a mixed solution of 17.7 g of 2-chloro-9H-carbazole, 22 g of iodobenzene, 20 g of a copper powder, 43 g of potassium carbonate and 200 ml of dimethylformamide was heated/stirred at 140° C. for 16 hours under a nitrogen flow. The solution was cooled to room temperature, 50 ml of ethyl acetate was added, and the mixture was filtered with Celite. To the resultant filtrate was added a saturated aqueous ammonium chloride solution, and the mixture was stirred for a while, and then extracted with ethyl acetate and hexane. The extract was dried over magnesium sulfate, and then evaporated. The concentrate was purified by silica gel column chromatography and vacuum-dried to obtain 14 g of 2-chloro-9-phenyl-9H-carbazole.
Reaction SMILES: O1[CH:5]=[CH:4][CH:3]=[CH:2]1.[C:6]12[CH2:12][C:9](=[CH:10][CH:11]=1)[C:8]1C=CC=C[C:7]2=1>>[CH:2]1[C:3]2[C:4](=[CH:5][C:8]3[C:9]([CH:2]=2)=[CH:10][C:11]2[C:6](=[CH:12][C:11]4[C:6]([CH:12]=2)=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:7]=3)[CH:5]=[CH:4][CH:3]=1
Reactant: C1=C2CC(=C1)c1ccccc12
Reactant: c1ccoc1
Product: c1ccc2cc3cc4cc5ccccc5cc4cc3cc2c1
Temperature: 128 °C
Yield: 40 %

Procedure:
In summary, a new stable and soluble pentacene precursor 2 was synthesized in 40% yield from the cycloaddition of a furan derivative 3 and a benzonorbornadiene 4. Compound 2 releases a unit of CO upon heating at 128° C. or by irradiation with UV light (366 nm) to produce pentacene in nearly quantitative yield. Thin films of pentacene were prepared by spin-coating followed by thermal annealing, and found to display typical FET characteristics.
Reaction SMILES: [H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].[CH3:14][C:15]1([S:18]([N:21]2[CH2:24][C:23](=O)[CH2:22]2)(=[O:20])=[O:19])[CH2:17][CH2:16]1.[Na+].[Cl-]>O1CCCC1.O>[CH3:14][C:15]1([S:18]([N:21]2[CH2:24][C:23](=[CH:5][C:3]#[N:4])[CH2:22]2)(=[O:19])=[O:20])[CH2:17][CH2:16]1
Reactant: CCOP(=O)(CC#N)OCC
Reactant: CC1(S(=O)(=O)N2CC(=O)C2)CC1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC1(S(=O)(=O)N2CC(=CC#N)C2)CC1
Reaction time: 0.75 h
Yield: 100 %

Procedure:
To a mixture of sodium hydride (60% dispersion in mineral oil, 17 mg, 0.42 mmol) in tetrahydrofuran (2 mL) at 0° C. was added diethyl cyanomethylphosphonate (70 μL, 0.43 mmol) dropwise. The mixture was then allowed to reach room temperature and stir for a further 45 minutes. A solution of 1-[(1-methylcyclopropyl)sulfonyl]azetidin-3-one (prepared in Step 5) in tetrahydrofuran (1.0 mL) was added and the mixture was allowed to stir at ambient temperature for 16 hours. Into the reaction was added water and solid NaCl, and the product was extracted with three portions of ethyl acetate. The combined extracts were dried over sodium sulfate, decanted and concentrated to afford product (71 mg, 100%), used without further purification in Step 7.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8](=[O:30])[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19][O:20][CH3:21])=[C:14]([F:29])[CH:13]=3)[O:11][C:6]=2[C:5]([F:31])=[CH:4][C:3]=1[F:32].[H-].[Na+].Br[CH2:36][CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40].O>CN(C)C=O>[C:25]([O:24][C:22]([N:18]([C:15]1[CH:16]=[CH:17][C:12]([C:10]2[O:11][C:6]3[C:5]([F:31])=[CH:4][C:3]([F:32])=[C:2]([NH:1][CH2:36][CH2:37][CH:38]=[C:39]([CH3:41])[CH3:40])[C:7]=3[C:8](=[O:30])[CH:9]=2)=[CH:13][C:14]=1[F:29])[CH2:19][O:20][CH3:21])=[O:23])([CH3:27])([CH3:28])[CH3:26]
Reactant: CC(C)=CCCBr
Reactant: COCN(C(=O)OC(C)(C)C)c1ccc(-c2cc(=O)c3c(N)c(F)cc(F)c3o2)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COCN(C(=O)OC(C)(C)C)c1ccc(-c2cc(=O)c3c(NCCC=C(C)C)c(F)cc(F)c3o2)cc1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 37.9 %

Procedure:
2.70 g (6.00 mmol) of the above 5-amino-2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-4H-1-benzopyran-4-one was dissolved in 60 mL of dimethylformamide under argon atmosphere, 480 mg (12.0 mmol) of sodium hydride (60% oil dispersion) and 4.0 mL (30 mmol) of 5-bromo-2-methyl-2-pentene were added under ice-cooling and the mixture was stirred at room temperature for 18 hours. The reaction solution was cooled on ice, water was added and the mixture was extracted twice with ethyl acetate. The organic layer was washed twice with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:acetonitrile=30:1) to give 1.21 g of 2-[4-[N-(tert-butoxycarbonyl)-N-methoxymethylamino]-3-fluorophenyl]-6,8-difluoro-5-(4-methyl-3-pentenylamino)-4H-1-benzopyran-4-one (yield: 38%).
Reaction SMILES: [CH3:1][C:2]1[N:6]([C@@H:7]2[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9][CH2:8]2)[C:5]2[CH:14]=[CH:15][C:16]([CH3:18])=[CH:17][C:4]=2[N:3]=1.[C:19]([C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[CH2:26][C@H:25]([CH:30]=O)[CH2:24]2)#[N:20]>>[CH3:1][C:2]1[N:6]([C@@H:7]2[CH2:8][CH2:9][C@H:10]([NH:13][CH2:30][C@@H:25]3[CH2:24][C:23]4[C:27](=[CH:28][CH:29]=[C:21]([C:19]#[N:20])[CH:22]=4)[CH2:26]3)[CH2:11][CH2:12]2)[C:5]2[CH:14]=[CH:15][C:16]([CH3:18])=[CH:17][C:4]=2[N:3]=1
Reactant: N#Cc1ccc2c(c1)C[C@@H](C=O)C2
Reactant: Cc1ccc2c(c1)nc(C)n2[C@H]1CC[C@@H](N)CC1
Product: Cc1ccc2c(c1)nc(C)n2[C@H]1CC[C@@H](NC[C@H]2Cc3ccc(C#N)cc3C2)CC1

Procedure:
This compound was prepared from the hydrochloride salt of cis-4-(2,5-dimethyl-benzoimidazol-1-yl)-cyclohexylamine and (S)-5-cyano-indan-2-carbaldehyde. 1H-NMR is consistent with the assigned structure, LC-MS showed a single peak, C26H30N4 (m/e) calcd 398.2470, obsd 399.3 (M+H).