Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[C:5]([NH:7][NH:8][C:9](=O)[CH:10]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=O.O(C1C=CC(P2(=S)SP(=S)(C3C=CC(OC4C=CC=CC=4)=CC=3)[S:46]2)=CC=1)C1C=CC=CC=1>C1COCC1>[CH3:1][O:2][C:3]1[CH:31]=[CH:30][CH:29]=[CH:28][C:4]=1[C:5]1[S:46][C:9]([CH:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[N:8][N:7]=1
Reactant: COc1ccccc1C(=O)NNC(=O)C(C(=O)OCc1ccccc1)c1ccccc1
Reactant: S=P1(c2ccc(Oc3ccccc3)cc2)SP(=S)(c2ccc(Oc3ccccc3)cc2)S1
Solvent: C1CCOC1
Product: COc1ccccc1-c1nnc(C(C(=O)OCc2ccccc2)c2ccccc2)s1
Reaction time: 8 h
Yield: 76.5 %

Procedure:
To a solution of compound 36 (539 mg, 1.02 mmol) in THF (4 mL) was added 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (539 mg, 1.02 mmol) and the reaction stirred overnight. The crude material was concentrated and purified by silica gel column chromatography with gradient of ethyl acetate (5-40%) in hexane to afford compound 37 (325 mg, 76%) as a white solid. LRMS (ESI): (calc) 416.4, (found) 417.4 (MH)+.
Reaction SMILES: [H-].[Na+].[CH2:3]1[C:15]2[NH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]=2[CH:6]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:5][CH2:4]1>CN(C)C=O>[C:16]([N:14]1[C:15]2[CH2:3][CH2:4][CH2:5][CH:6]([C:16]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:17])[C:7]=2[C:8]2[C:13]1=[CH:12][CH:11]=[CH:10][CH:9]=2)(=[O:17])[C:6]1[CH:7]=[CH:15][CH:3]=[CH:4][CH:5]=1
Reactant: O=C(OCc1ccccc1)C1CCCc2[nH]c3ccccc3c21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)C1CCCc2c1c1ccccc1n2C(=O)c1ccccc1
Reaction time: 2 h

Procedure:
To 0.85 g. sodium hydride in 150 ml. of dry dimethylformamide was added, portionwise, 9 g. of benzyl 1,2,3,4-tetrahydrocarbazole-4-carboxylate. The mixture was heated on a steam bath for 15 minutes, the heat was removed, 4 ml. benzoyl chloride was added dropwise to the still hot mixture and heating was resumed for two hours. The mixture, after standing overnight at room temperature, was poured into water containing 4 ml. glacial acetic acid and the resulting mixture was extracted with ether. The ether extract was washed with sodium bicarbonate solution and water, dried, and evaporated to dryness. The resulting residue in 50 ml. dimethylformamide was again treated with 0.42 g. sodium hydride and 2 ml. benzoyl chloride and worked up as described above and the resulting crude product was chromatographed on a 45 mm. by 620 mm. silica gel column using as eluant hexane and hexane containing increasing amounts of ether. There was thus obtained with 7.5% ether in hexane, after evaporation to dryness and recrystallization, 4.6 g. of the title compound; m.p. 107°-109°C. (methyl alcohol).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[C:11]1[C:12]([S:17][CH3:18])=[N:13][CH:14]=[N:15][CH:16]=1.[N+:20]([O-])([OH:22])=[O:21].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[CH3:1][C:2]1([CH3:19])[CH2:10][C:9]2[C:4](=[CH:5][C:6]([N+:20]([O-:22])=[O:21])=[CH:7][CH:8]=2)[CH:3]1[C:11]1[C:12]([S:17][CH3:18])=[N:13][CH:14]=[N:15][CH:16]=1
Reactant: CSc1ncncc1C1c2ccccc2CC1(C)C
Reactant: O=[N+]([O-])O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CSc1ncncc1C1c2cc([N+](=O)[O-])ccc2CC1(C)C

Procedure:
To a solution of 30 g (0.11 mol) of 5-(2,2-dimethylindan-1-yl)-4-methylthiopyrimidine in 500 mL of dichloromethane was added dropwise 100 mL of 90 percent nitric acid. After 1 hr the reaction mixture was poured onto a large volume of ice. The mixture was slowly neutralized with solid potassium carbonate and was then extracted with ether. The organic phase was recovered, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain 36 g of a tan solid. This was recrystallized from 400 mL of ethyl acetate to obtain 12 g of the title compound as a white solid melting at 167°-168° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][C:8](Br)=[CH:9][CH:10]=2)[C:5](=[O:13])[CH2:4][CH2:3]1.[CH:15]([C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1)=[CH2:16].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1([CH3:14])[CH2:3][CH2:4][C:5](=[O:13])[C:6]2[CH:7]=[C:8](/[CH:16]=[CH:15]/[C:17]3[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=3)[CH:9]=[CH:10][C:11]1=2
Reactant: C=Cc1ccc(C(=O)OCC)cc1
Reactant: CC1(C)CCC(=O)c2cc(Br)ccc21
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(/C=C/c2ccc3c(c2)C(=O)CCC3(C)C)cc1
Temperature: 95 °C

Procedure:
To a solution of 520.0 mg (2.00 mmol) of 3,4-dihydro-4,4-dimethyl-7-bromo-1(2H)-naphthalenone (Compound B) and 510.0 mg (2.90 mmol) of ethyl 4-vinylbenzoate in 4.0 ml of triethylamine (degassed by sparging with argon for 25 minutes), was added 124.0 mg (0.40 mmol) of tris(2-methylphenyl) phosphine, followed by 44.0 mg (0.20 mmol) of palladium(II)acetate. The resulting solution was heated to 95° C. for 2.5 hours, cooled to room temperature, and concentrated under reduced pressure. Purification by column chromatography (10% EtOAc/hexanes) afforded the title compound as a colorless solid. 1H NMR (CDCl3): δ 8.19 (1H, d, J=2.0 Hz), 8.03 (2H, d, J=8.4 Hz), 7.69 (1H, dd, J=2.0, 8.2 Hz), 7.57 (2H, d, J=8.4 Hz), 7.45 (1H, d, J=8.2 Hz), 7.20 (2H, s), 4.39 (2H, q, J=7.1 Hz), 2.76 (2H, t, J=6.5 Hz), 2.04 (2H, t, J=6.5 Hz), 1.41(3H, t, J=7.1 Hz, and 6H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][CH2:19]CS([O-])(=O)=O)=[N:14][O:15][N:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[F:8].CCN(C(C)C)C(C)C.[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([C:12]2[C:13]([CH2:17][CH2:18][CH2:19][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[N:14][O:15][N:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: C1COCCN1
Reactant: O=C(Nc1ccc(F)c(Cl)c1)c1nonc1CCCCS(=O)(=O)[O-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C(Nc1ccc(F)c(Cl)c1)c1nonc1CCCN1CCOCC1
Temperature: 70 °C
Yield: 53.2 %

Procedure:
3-(4-[(3-Chloro-4-fluorophenyl)amino]carbonyl-1,2,5-oxadiazol-3-yl)propylmethanesulfonate (19 mg, 0.051 mmol) was dissolved in anhydrous ACN (100 μL,) followed by addition of DIPEA (44 μL, 0.26 mmol) and morpholine (6.7 μL, 76.8 μmol). The reaction was stirred and heated at 70° C. for 3 h. The reaction was concentrated and purified with silica gel chromatography (60-100% ethyl acetate/hex) to give the desired product (10 mg, 54%). LCMS for C16H19ClFN4O3(M+H)+: m/z=369.1.
Reaction SMILES: [OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][N:24](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][NH:24][C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(NC(=O)N[C@@H](c3ccccc3)C(C)(C)O)nc(CO)c12
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1n[nH]c2cc(NC(=O)N[C@@H](c3ccccc3)C(C)(C)O)nc(CO)c12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (533 mg, 0.849 mmol) was dissolved in DCM (3 ml), charged with triethylsilane (0.271 ml, 1.698 mmol) followed by TFA (3.27 ml, 42.5 mmol) and allowed to stir for 1 h at rt. The solvents were removed in vacuo and the residue was dissolved in 25 mL 10:1 EtOAc/MeOH and washed with 20 mL saturated sodium bicarbonate. The aq. was extracted 1×15 mL EtOAc and the combine organics were washed with brine, dried over sodium sulfate, concentrated vacuo and purified on silica gel 5-15% MeOH/DCM to provide (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (110) as a white solid. MS: [M+H]+ m/z 386. 1H NMR (600 MHz, dmso) δ 12.00 (s, 1H), 9.20 (s, 1H), 7.31 (m, 2H), 7.25 (m, 2H), 7.15 (m, 1H), 7.07 (br s, 1H), 5.00 (t, J=6.0, 1H), 4.74 (d, J=6.0, 2H), 4.68 (s, 1H), 4.59 (d, J=9.0, 1H), 3.93 (s, 3H), 1.13 (s, 3H), 1.12 (s, 3H).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][N:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:17](Cl)=[O:18]>>[O:1]([C:8]1[CH:9]=[C:10]([O:14][C:17](=[O:18])[N:16]([CH3:15])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: Oc1cccc(Oc2ccccc2)c1
Product: CN(C(=O)Oc1cccc(Oc2ccccc2)c1)c1ccccc1

Procedure:
The title product was prepared from 3-phenoxyphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil). HPLC-MS: m/z=320.1 (M+1); Rt: 5.16 min.
Reaction SMILES: [CH3:1][C:2]1[C:14]([OH:15])=[C:13]([CH3:16])[CH:12]=[C:11]2[C:3]=1[CH2:4][CH2:5][C:6]1([O:10]2)[CH2:9][CH2:8][CH2:7]1.S(Cl)([Cl:20])(=O)=O.C(OCC)(=O)C>C(OCC)C>[Cl:20][C:12]1[C:13]([CH3:16])=[C:14]([OH:15])[C:2]([CH3:1])=[C:3]2[C:11]=1[O:10][C:6]1([CH2:7][CH2:8][CH2:9]1)[CH2:5][CH2:4]2
Reactant: Cc1cc2c(c(C)c1O)CCC1(CCC1)O2
Reactant: O=S(=O)(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: Cc1c(O)c(C)c2c(c1Cl)OC1(CCC1)CC2
Reaction time: 2 h

Procedure:
To a solution of 5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol (350 mg) in ethyl ether (6 mL) was added sulfonyl chloride (0.154 mL, 260 mg) dropwise at room temperature under nitrogen. After 2 hours, ethyl acetate was added, washed with an aqueous sodium bicarbonate solution, water and brine, and dried. Evaporation and chromatography (silica gel hexane-ethyl acetate 0% to 4%, hexane-dichloromethane 5% to 20%) yielded the desired compound. Crystallization with hexane gave colorless crystals of 8-chloro-5,7-dimethyl-3,4-dihydrospiro[chromene-2,1′-cyclobutan]-6-ol (60 mg). 1H-NMR (300 MHz, CDCl3) δ=4.29 (s, 1H), 2.67 (t, J=6.6 Hz, 2H), 2.35-1.80 (m, 13H), 1.75-1.60 (m, 1H) ppm. 13C-NMR (75 MHz, CDCl3) δ=145.2, 143.6, 120.9, 120.1, 119.9, 119.7, 77.3, 33.8, 29.2, 20.8, 13.2, 12.5, 11.5 ppm. MS: (m/z)=253 (100, M+H+), 275 (23, M+Na+).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][CH:8]=[N:7][C:6]=2[CH:10]=1.[CH3:11][N:12](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[S:9]1[C:5]2[CH:4]=[CH:3][C:2]([C:11]#[N:12])=[CH:10][C:6]=2[N:7]=[CH:8]1
Reactant: Brc1ccc2scnc2c1
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: N#Cc1ccc2scnc2c1
Temperature: 80 °C

Procedure:
Into a mixture of 5-bromo-1,3-benzothiazole (300 mg, 1.40 mmol, 1.00 equiv) and zinc cyanide (131.6 mg, 0.80 equiv) in N,N-dimethylformamide (6.0 mL) was added Pd(PPh3)4 (80.9 mg, 0.07 mmol, 0.05 equiv) and nitrogen was bubbled for 5 min. The resulting mixture was heated overnight at 80° C., quenched by water (15.0 mL), and extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with brine (2×15 mL) and dried over Na2SO4. After filtered and concentrated under reduced pressure, the residue was purified by flash chromatography on silica gel, eluting with a mixture of 5-10% ethyl acetate in petroleum ether to afford the title compound as a light yellow solid. MS m/z [M+H]+ (ESI): 161.