Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:6]=[S:7]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22]2[N:27]=[C:26]([NH:28][C@H:29]([CH3:32])[CH2:30][OH:31])[C:25]([C:33]3[S:34][CH:35]=[CH:36][CH:37]=3)=[CH:24][N:23]=2)=[CH:17][CH:16]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8])=O)C.CC[O-].[Na+]>>[OH:31][CH2:30][C@H:29]([NH:28][C:26]1[C:25]([C:33]2[S:34][CH:35]=[CH:36][CH:37]=2)=[CH:24][N:23]=[C:22]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([S:7]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)(=[NH:6])=[O:8])=[CH:16][CH:17]=2)[N:27]=1)[CH3:32]
Reactant: CCOC(=O)N=S(=O)(c1ccccc1)c1ccc(Nc2ncc(-c3cccs3)c(N[C@H](C)CO)n2)cc1
Agent: CC[O-]
Agent: [Na+]
Product: C[C@H](CO)Nc1nc(Nc2ccc(S(=N)(=O)c3ccccc3)cc2)ncc1-c1cccs1
Yield: 40 %

Procedure:
In the reaction of (RS)—N-(ethoxycarbonyl)-S-(4-{[4-{[(R)-2-hydroxy-1-methyl-ethyl]amino}-5-(2-thienyl)pyrimidine-2-yl]amino}phenyl)-S-phenylsulfoximide with sodium ethylate according to procedure 14, the desired product is obtained in 40% yield after chromatographic purification (silica gel, dichloromethane/ethanol (0-10% ethanol)).
Reaction SMILES: C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:36]1[C:41]([CH:42]2[CH2:44][CH2:43]2)=[CH:40][CH:39]=[CH:38][N:37]=1.[OH:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]2[N:57]([CH3:58])[C:56](=[O:59])[N:55]([CH2:60][O:61][CH2:62][CH2:63][Si:64]([CH3:67])([CH3:66])[CH3:65])[C:54](=[O:68])[C:53]=2[CH3:69])=[C:48]([CH3:70])[CH:47]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:42]1([C:41]2[C:36]([O:45][C:46]3[CH:51]=[CH:50][C:49]([C:52]4[N:57]([CH3:58])[C:56](=[O:59])[N:55]([CH2:60][O:61][CH2:62][CH2:63][Si:64]([CH3:67])([CH3:66])[CH3:65])[C:54](=[O:68])[C:53]=4[CH3:69])=[C:48]([CH3:70])[CH:47]=3)=[N:37][CH:38]=[CH:39][CH:40]=2)[CH2:44][CH2:43]1
Reactant: Cc1cc(O)ccc1-c1c(C)c(=O)n(COCC[Si](C)(C)C)c(=O)n1C
Reactant: Clc1ncccc1C1CC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1c(C)c(C)c(P(C(C)(C)C)C(C)(C)C)c(-c2c(C(C)C)cc(C(C)C)cc2C(C)C)c1C
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1cc(Oc2ncccc2C2CC2)ccc1-c1c(C)c(=O)n(COCC[Si](C)(C)C)c(=O)n1C
Temperature: 120 °C
Reaction time: 5 h

Procedure:
Palladium(II) acetate (61 mg, 0.27 mmol) and di-tert-butyl[3,4,5,6-tetramethyl-2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (130 mg, 0.27 mmol) were added to a mixture of C6 (615 mg, 4.00 mmol), C5 (1.0 g, 2.6 mmol) and cesium carbonate (2.6 g, 8.0 mmol) in 1,4-dioxane (25 mL). The reaction mixture was stirred at 120° C. under microwave irradiation for 5 hours, then diluted with ethyl acetate (50 mL) and filtered. After removal of solvents in vacuo, the residue was purified via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in petroleum ether) to provide the product as a yellow gum. Yield: 900 mg, 1.8 mmol, 69%. LCMS m/z 494.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J=4.8, 1.8 Hz, 1H), 7.30 (dd, J=7.4, 1.8 Hz, 1H), 7.11-7.14 (m, 1H), 7.08-7.10 (m, 2H), 7.01 (dd, J=7.5, 4.8 Hz, 1H), 5.51 (AB quartet, JAB=9.3 Hz, ΔνAB=3.8 Hz, 2H), 3.74-3.80 (m, 2H), 3.08 (s, 3H), 2.18 (s, 3H), 2.16-2.24 (m, 1H), 1.70 (s, 3H), 1.00-1.06 (m, 4H), 0.74-0.79 (m, 2H), 0.03 (s, 9H).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:11][C:9](=[O:10])[C:5](=[C:6]([CH3:8])[CH3:7])[CH2:4][CH2:3]1.[CH3:12][Al](C)C.C[Si](Cl)(C)C.O>C1COCC1.C1(C)C=CC=CC=1>[C:6]([CH:5]1[CH2:4][CH2:3][CH:2]([CH3:1])[CH2:11][C:9]1=[O:10])([CH3:12])([CH3:7])[CH3:8]
Reactant: CC(C)=C1CC[C@@H](C)CC1=O
Reactant: C[Al](C)C
Agent: C[Si](C)(C)Cl
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Solvent: O
Product: CC1CCC(C(C)(C)C)C(=O)C1
Yield: 86.2 %

Procedure:
1.52 g (10 mmol) of pulegone (2-isopropylidene-5-methylcyclohexanone) and 14.3 mg (0.1 mmol) of CuBr in 10 ml of dry THF are introduced at room temperature. 9.5 ml (11 mmol) of 10% trimethylaluminum in toluene and 1.3 g (12 mmol) of trimethylsilyl chloride are added at 0° C. It is stirred for 5 more hours at room temperature, hydrolyzed with 5 ml of water and extracted twice with 30 ml of ether each, and the organic phases are combined. After the solvent is evaporated, the product is distilled at 10 torr and 120° C. in a bulb tube. 1.45 g (86% of theory) of 2-tert-butyl-5-methylcyclohexanone is obtained.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[O:7][CH2:6][C:5]2=[CH:8][C:9]([NH2:11])=[N:10][N:4]2[CH2:3]1.Br[C:14]1[C:15](=[O:22])[N:16]([CH3:21])[N:17]=[C:18]([Cl:20])[CH:19]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:20][C:18]1[CH:19]=[C:14]([NH:11][C:9]2[CH:8]=[C:5]3[CH2:6][O:7][C:2]([CH3:12])([CH3:1])[CH2:3][N:4]3[N:10]=2)[C:15](=[O:22])[N:16]([CH3:21])[N:17]=1
Reactant: CC1(C)Cn2nc(N)cc2CO1
Reactant: Cn1nc(Cl)cc(Br)c1=O
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cn1nc(Cl)cc(Nc2cc3n(n2)CC(C)(C)OC3)c1=O
Temperature: 100 °C
Yield: 45 %

Procedure:
A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 330g (250 mg, 1.5 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (669 mg, 3.0 mmol), Pd2(dba)3 (137 mg, 0.15 mmol), Xantphos (173 mg, 0.30 mmol), Cs2CO3 (978 mg, 3.0 mmol), and 1,4-dioxane (20 mL). After three cycles of vacuum/argon flush, the mixture was heated at 100° C. for 3 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and washed with ethyl acetate to afford 330h as a yellow solid (209 mg, 45%). MS-ESI: [M+H]+ 310.1
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([C:11]2[N:12]=[C:13]([CH3:17])[S:14][C:15]=2[NH2:16])=[O:10])[CH:5]=[CH:6][CH:7]=1.Br[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([C:11]2[N:12]=[C:13]([CH3:17])[S:14][C:15]=2[NH:16][C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1nc(C(=O)Nc2cccc(Cl)c2)c(N)s1
Reactant: Brc1ccncc1
Product: Cc1nc(C(=O)Nc2cccc(Cl)c2)c(Nc2ccncc2)s1

Procedure:
The title compound was prepared by reaction of 5-amino-2-methyl-thiazole-4-carboxylic acid (3-chloro-phenyl)-amide (prepared as illustrated in example 127) with 4-bromopyridine, as follows.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:42])[CH2:5][N:6]([C:15]([C:17]1([CH2:33][O:34]CC2C=CC=CC=2)[CH2:20][CH2:19][N:18]1[C:21](=[O:32])[CH2:22][C:23]1[C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[S:26][CH:27]=1)=[O:16])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1)[CH3:2].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:42])[CH2:5][N:6]([C:15]([C:17]1([CH2:33][OH:34])[CH2:20][CH2:19][N:18]1[C:21](=[O:32])[CH2:22][C:23]1[C:24]2[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=2[S:26][CH:27]=1)=[O:16])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1)[CH3:2]
Reactant: CCOC(=O)CN(Cc1ccc(Cl)cc1)C(=O)C1(COCc2ccccc2)CCN1C(=O)Cc1csc2ccccc12
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)CN(Cc1ccc(Cl)cc1)C(=O)C1(CO)CCN1C(=O)Cc1csc2ccccc12
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of [[1-(2-benzo[b]thiophen-3-yl-acetyl)-2-benzyloxymethyl-azetidine-2-carbonyl]-(4-chloro-benzyl)-amino]-acetic acid ethyl ester, Intermediate 163 (1 eq.) in DCM at 0° C. was added BBr3. The reaction was stirred at 0° C. for 2 h. The crude was diluted with DCM and poured into a saturated aqueous solution of NaHCO3. The layers were separated, the organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 100/0 to 95/5) to afford [[1-(2-benzo[b]thiophen-3-yl-acetyl)-2-hydroxymethyl-azetidine-2-carbonyl]-(4-chloro-benzyl)-amino]-acetic acid ethyl ester.
Reaction SMILES: [N:1]([C@H:4]([CH2:21][CH3:22])[C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[N+]=[N-]>CO.[Pd]>[NH2:1][C@H:4]([CH2:21][CH3:22])[C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: CC[C@@H](N=[N+]=[N-])[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CO
Product: CC[C@@H](N)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C
Yield: 92.1 %

Procedure:
A solution of tert-butyl (2S,3R)-3-azido-1-cyclohexylpentan-2-ylcarbamate (64 mg, 0.21 mmol) and 10% Pd/C in methanol (20 mL) was hydrogenated at 40 psi for 1 h. The catalyst was filtered off, and the filtrate concentrated to give tert-butyl (2S,3R)-3-amino-1-cyclohexylpentan-2-ylcarbamate (55 mg, 93%). MS ESI +ve m/z 285 (M+H).
Reaction SMILES: [C:1]([O:5][CH:6]([CH2:21][S:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:7][S:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:4])[CH:2]=[CH2:3].[CH2:35]([SH:47])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46].Cl>C(O)C.O>[CH2:35]([S:47][CH2:3][CH2:2][C:1]([O:5][CH:6]([CH2:7][S:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:21][S:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:4])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46]
Reactant: C=CC(=O)OC(CSCCCCCCCCCCCC)CSCCCCCCCCCCCC
Reactant: CCCCCCCCCCCCS
Agent: Cl
Solvent: CCO
Solvent: O
Product: CCCCCCCCCCCCSCCC(=O)OC(CSCCCCCCCCCCCC)CSCCCCCCCCCCCC

Procedure:
A solution of 23.0 grams of 1,3-bis(dodecylthio)-2-propyl acrylate, 9.05 grams of dodecanethiol and 1 milliliter of "Triton B" in 75 milliliters of ethanol was heated under reflux for 6 hours. The reaction mixture was allowed to cool and was then poured into a solution of 5 milliliters of concentrated hydrochloric acid in 300 milliliters of water. The light colored oil which precipitated crystallized on stirring and the crystalline solid was filtered off and allowed to dry. The product, 1,3-bis(dodecylthio)-2-propyl 3-(dodecylthio)propionate, weighed 31.5 grams and melted at 31°-32° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[SH:10].[C:11](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[S:10][CH3:11]
Reactant: COc1ccc(Br)c(S)c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1ccc(Br)c(SC)c1
Reaction time: 2 h

Procedure:
The product of step (c) above (140 mg) was dissolved in dry dimethyl formamide (2 ml). Potassium carbonate (114 mg) was added followed by methyl iodide (47 ml). The mixture was stirred for 2 hours, poured onto water and extracted with ethyl acetate. The ethyl acetate was washed with water and brine then dried and evaporated to leave the subtitle compound as a pale brown oil MS MW 232/4 bp 232.