Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[C:5]([C:8]#[N:9])[C:6]#[N:7])[CH3:4].[NH:10]([C:12]1[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:15]=[C:14]([C:30]([F:33])([F:32])[F:31])[N:13]=1)[NH2:11]>CO>[NH2:9][C:8]1[N:10]([C:12]2[C:17]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:15]=[C:14]([C:30]([F:33])([F:32])[F:31])[N:13]=2)[N:11]=[C:3]([CH3:4])[C:5]=1[C:6]#[N:7]
Reactant: NNc1nc(C(F)(F)F)nc(-c2ccccc2)c1-c1ccccc1
Reactant: COC(C)=C(C#N)C#N
Solvent: CO
Product: Cc1nn(-c2nc(C(F)(F)F)nc(-c3ccccc3)c2-c2ccccc2)c(N)c1C#N

Procedure:
1-Methoxyethylidene malononitrile (0.17 g, 1.36 mmol) (prepared from malononitrile and triethyl orthoacetate by heating with acetic anhydride) was heated with 4-hydrazino-5,6-diphenyl-2-(trifluoromethyl)pyrimidine (0.15 g, 0.45 mmol) in methanol (6 ml), overnight at 60-65° C. The solid that separated out from the reaction mixture was filtered and washed with methanol (5 ml), to yield the title compound. 1H-NMR (DMSO-d6) δ: 1.97 (s, 3H), 6.97 (br, 2H, D2O exchangeable), 7.07 (d, 2H), 7.26-7.38 (m, 7H), 7.40-7.41 (m, 1H); MS m/z: 421.1 (M++1).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([C:14]1[C:18]2[CH2:19][CH2:20][CH2:21][C:22]3[C:23](=[N:24][C:25]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]5)=[CH:31][C:30]=4[O:42][CH3:43])=[N:26][CH:27]=3)[C:17]=2[NH:16][N:15]=1)=[O:13])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:51][CH3:52]>CN(C=O)C>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[C:4]=1[NH:11][C:12]([C:14]1[C:18]2[CH2:19][CH2:20][CH2:21][C:22]3[C:23](=[N:24][C:25]([NH:28][C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]5)=[CH:31][C:30]=4[O:42][CH3:43])=[N:26][CH:27]=3)[C:17]=2[N:16]([CH2:51][CH3:52])[N:15]=1)=[O:13])[CH3:2]
Reactant: CCc1cccc(CC)c1NC(=O)c1n[nH]c2c1CCCc1cnc(Nc3ccc(N4CCN(C)CC4)cc3OC)nc1-2
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCc1cccc(CC)c1NC(=O)c1nn(CC)c2c1CCCc1cnc(Nc3ccc(N4CCN(C)CC4)cc3OC)nc1-2
Temperature: 25 °C
Reaction time: 12 h
Yield: 44.8 %

Procedure:
To a solution of N-(2,6-diethylphenyl)-9-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-1,4,5,6-tetrahydropyrazolo[4′,3′:6,7]cyclohepta[1,2-d]pyrimidine-3-carboxamide (0.065 g, 0.11 mmol) in DMF (1.1 mL), Cs2CO3 (0.073 g, 0.22 mmol) and bromoethane (0.008 mL, 0.11 mmol) were added. The mixture was stirred at room temperature for 12 h, solvent was removed under vacuo, then DCM (10 mL) was added and the organic phase washed with water (2×15 mL). The organic fraction was, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by flash chromatography on silica gel (eluant: DCM/MeOH95/5) provided 30 mg (30%) of the title compound as a pale yellow solid.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[NH:7][N:6]=[CH:5]2.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([I:1])=[C:10]([CH3:11])[CH:9]=3)[CH:5]=[N:6]2)=[CH:15][CH:14]=1
Reactant: Cc1cc2[nH]ncc2cc1I
Reactant: OB(O)c1ccc(F)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cc2c(cnn2-c2ccc(F)cc2)cc1I
Yield: 51.1 %

Procedure:
5-Iodo-6-methylindazole (1.3 g, 5.0 mmol), p-fluorobenzeneboronic acid (1.4 g, 10 mmol), anhydrous copper(II) acetate (1.4 g, 7.5 mmol) and pyridine (0.80 mL, 10 mmol) were stirred in dichloromethane (30 mL) overnight. Additional portions of p-fluorobenzeneboronic acid (0.47 g, 3.4 mmol), anhydrous copper(II) acetate (0.45 g, 2.5 mmol) and pyridine (0.27 mL, 3.4 mmol) were added. The mixture was filtered through celite after stirring for an additional night. The filtrate was concentrated and purified by column chromatography (SiO2, toluene) to give the subtitle compound (0.90 g, 51%) as a light orange powder.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[C:9]([CH2:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][CH2:14][N:13]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[N:10]=[C:4]2[N:3]=1.C1C(=O)N([Cl:32])C(=O)C1>C(Cl)Cl>[Cl:32][C:8]1[N:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[N:3][C:4]2=[N:10][C:9]=1[CH2:11][C@@H:12]1[CH2:17][CH2:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]
Reactant: O=C1CCC(=O)N1Cl
Reactant: Cc1ccn2cc(C[C@@H]3CCCCN3C(=O)OC(C)(C)C)nc2n1
Solvent: ClCCl
Product: Cc1ccn2c(Cl)c(C[C@@H]3CCCCN3C(=O)OC(C)(C)C)nc2n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 43.4 %

Procedure:
To a solution of 1,1-dimethylethyl (2S)-2-[(7-methylimidazo[1,2-a]pyrimidin-2-yl)methyl]-1-piperidinecarboxylate (0.350 g, 0.53 mmol) in DCM (5 ml) was added NCS (0.071 g, 0.53 mmol) and the reaction mixture was stirred for 1.5 h at rt. The solvent was evaporated and the residue purified by cromatography on silica gel (Biotage, NH phase 25+M, Cy/EtOAc from 100/0 to 50/50). Collected fractions gave the title compound (0.085 g, 0.23 mmol, 44% yield) as a colourless solid. UPLC: rt=0.70, peak observed: 365 (M+1, 100%) and 367 (M+1, 33%). C18H25ClN4O2 requires 365.
Reaction SMILES: [BH4-].[CH2:2]([C:9]1[N:10]([CH3:15])[C:11]([SH:14])=[N:12][N:13]=1)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].I[C:17]1[CH:36]=[CH:35][C:20]([CH2:21][NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:25][CH:24]=2)=[C:19]([O:37][CH2:38][CH2:39][CH3:40])[CH:18]=1>O1CCCC1.C(O)C>[CH2:33]([O:32][C:30](=[O:31])[CH2:29][C:26]1[CH:27]=[CH:28][C:23]([NH:22][CH2:21][C:20]2[CH:35]=[CH:36][C:17]([S:14][C:11]3[N:10]([CH3:15])[C:9]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[N:13][N:12]=3)=[CH:18][C:19]=2[O:37][CH2:38][CH2:39][CH3:40])=[CH:24][CH:25]=1)[CH3:34]
Reactant: CCCCCCCc1nnc(S)n1C
Reactant: CCCOc1cc(I)ccc1CNc1ccc(CC(=O)OCC)cc1
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCCCCCc1nnc(Sc2ccc(CNc3ccc(CC(=O)OCC)cc3)c(OCCC)c2)n1C
Reaction time: 8 h

Procedure:
2.647 g (6.62 mmol, 3 eq) of resin-supported borohydride and 30 mg (0.06 mmol, 0.03 eq) of bis(bipyridine)dibromonickel (II) are added to a solution of 0.706 g (3.31 mmol, 1.5 eq) of 5-heptyl-4-methyl-4H-[1,2,4]-triazole-3-thiol in 10 ml of tetrahydrofuran/ethanol 5/5. To the suspension obtained there is added a solution of 100 mg (0.22 mmol, 1 eq) of ethyl [4-(4-iodo-2-propoxybenzylamino)phenyl]acetate in 10 ml of tetrahydrofuran/ethanol 5/5. The reaction mixture is stirred overnight under reflux. After returning to room temperature, the reaction medium is filtered, concentrated and then chromatographed on silica gel (heptane/ethyl acetate 40/60). After evaporation of the solvents, 0.750 g (63%) of the expected compound is recovered.
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([NH:7][CH3:8])=[CH:5][CH:4]=1)#[N:2].[C:11]1([N:17]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:18]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][C:26]([CH2:28]OC)=[N:25][C:24]=3[CH:31]=2)=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>ClCCl.C(O)C>[C:11]1([N:17]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:18]([C:20]2[CH:21]=[CH:22][C:23]3[S:27][C:26]([CH2:28][N:7]([C:6]4[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)[CH3:8])=[N:25][C:24]=3[CH:31]=2)=[O:19])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)CCN(C(=O)c1ccc2sc(COC)nc2c1)c1ccccc1
Reactant: CNc1ccc(C#N)cc1
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)CCN(C(=O)c1ccc2sc(CN(C)c3ccc(C#N)cc3)nc2c1)c1ccccc1
Yield: 57 %

Procedure:
Prepared analogously to Example 9e from 4-cyano-N-methylaniline and 2-methoxymethylbenzothiazole-5-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)amide. Yield: 57% of theory; Rf value: 0.46 (silica gel; dichloromethane/ethanol=19:1).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([OH:16])[C@@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].CS(O[CH2:28][C:29]1[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[C:31]([N:39]2[C:43]([CH3:44])=[N:42][N:41]=[N:40]2)[CH:30]=1)(=O)=O.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([O:16][CH2:28][C:29]2[CH:34]=[C:33]([C:35]([F:36])([F:37])[F:38])[CH:32]=[C:31]([N:39]3[C:43]([CH3:44])=[N:42][N:41]=[N:40]3)[CH:30]=2)[C@@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](O)[C@@H]1c1ccccc1
Reactant: Cc1nnnn1-c1cc(COS(C)(=O)=O)cc(C(F)(F)F)c1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nnnn1-c1cc(CO[C@H]2CCCN(C(=O)OC(C)(C)C)[C@H]2c2ccccc2)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.4 %

Procedure:
Sodium hydride (60% dispersion in mineral oil, 24 mg, 0.6 mmol) was added to a stirred, cooled (0° C.) solution of [2S,3S]-1-tert-butoxycarbonyl-2-phenylpiperidin-3-ol (138 mg, 0.5 mmol) in N,N-dimethylformamide (2 ml). The mixture was stirred at room temperature for 30 minutes, cooled in ice and 1-(methanesulfonyloxymethyl)-3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzene (168 mg, 0.5 mmol) in N,N-dimethylformamide (2 ml) was added. The mixture was stirred at room temperature for 66 hours, saturated aqueous sodium hydrogen carbonate (20 ml) and water (10 ml) were added and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (4×20 ml) and brine (20 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by MPLC on silica gel, eluting with ethyl acetate/hexane (40:60 increasing to 60:40) to give [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine as a pale yellow oil (133 mg, 51%), 1H (CDCl3) δ 7.69 (1H, s), 7.65 (1H, s), 7.52 (3H, m), 7.31-7.19 (3H, m), 5.68 (1H, br s), 4.77 (2H, s), 3.92 (2H, m), 2.78 (1H, m), 2.58 (3H, s), 2.00 (2H, m), 1.66 (2H, m), and 1.45 (9H, s). m/z 518 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([NH2:11])=[CH:6][CH:5]=2.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][NH:19][C:20]([C:22]2[S:30][C:29]3[C:24](=[N:25][CH:26]=[CH:27][C:28]=3Cl)[CH:23]=2)=[O:21])[CH:13]=1>>[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][NH:19][C:20]([C:22]2[S:30][C:29]3[C:24](=[N:25][CH:26]=[CH:27][C:28]=3[NH:11][C:7]3[CH:8]=[C:9]4[C:4](=[CH:5][CH:6]=3)[NH:3][C:2]([CH3:1])=[CH:10]4)[CH:23]=2)=[O:21])[CH:13]=1
Reactant: O=C(NCc1cccnc1)c1cc2nccc(Cl)c2s1
Reactant: Cc1cc2cc(N)ccc2[nH]1
Product: Cc1cc2cc(Nc3ccnc4cc(C(=O)NCc5cccnc5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from 2-methyl-1H-indol-5-ylamine and 7-chloro-thieno[3,2-b]pyridine-2-carboxylic acid (pyridin-3-ylmethyl)-amide by a procedure analogous to Example 1C. MS: 414 (MH+), HPLC Rf: 4.12 min.; HPLC purity: 97%.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N+:5]([O-])=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=1.CCN(CC)CC.O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:6]1[N:5]=[C:4]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=[C:2]([CH3:1])[CH:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc[n+]([O-])c(NC(=O)C(C)(C)C)c1
Solvent: CCN(CC)CC
Product: Cc1cc(Cl)nc(NC(=O)C(C)(C)C)c1
Temperature: 100 °C
Reaction time: 72 h
Yield: 16 %

Procedure:
To a solution of 4-methyl-2-pivalamidopyridine 1-oxide (3.0 g, 14 mmol) in POCl3 (30 mL) was added Et3N (6.0 mL, 43 mmol) drop-wise at 0° C. Then mixture was stirred at 100° C. for 3 days. The mixture was quenched with water, treated with aqueous NaOH to pH 8-9, and extracted with ethyl acetate (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4, evaporated under vacuum and purified by chromatography on silica gel (15% ethyl acetate in petroleum ether) to afford N-(6-chloro-4-methylpyridin-2-yl)pivalamide (520 mg, 16%). 1H NMR (CDCl3, 300 MHz) δ 8.03 (s, 1H), 7.93 (br s, 1H), 6.87 (s, 1H), 2.33 (s, 3H), 1.29 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:21])[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:5]([CH3:15])=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>>[CH3:15][C:5]1[N:4]([CH2:16][C:17]([O:19][CH3:20])=[O:18])[C:3](=[O:21])[C:2]([NH:1][C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])=[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: COC(=O)Cn1c(C)cc(Oc2ccccc2)c(N)c1=O
Product: COC(=O)Cn1c(C)cc(Oc2ccccc2)c(NC(=O)OCc2ccccc2)c1=O

Procedure:
2.5 g (7.9 mmol) of methyl 3-amino-6-methyl-2-oxo-4-phenoxy-1,2-dihydropyridine-1-acetate are treated with 1.7 ml (11.9 mmol) of phenylmethyl chloroformate under the conditions of Example 3.