Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH:8]([CH2:12][OH:13])[CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1.[C:14](=O)([O-])[O-].[K+].[K+].IC>C1COCC1>[Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][CH:8]([CH2:12][O:13][CH3:14])[CH2:7][C:6]=2[N:5]=[CH:4][N:3]=1
Reactant: OCC1CCc2c(Cl)ncnc2C1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CI
Product: COCC1CCc2c(Cl)ncnc2C1
Reaction time: 18 h
Yield: 35.3 %

Procedure:
To a slurry of (4-chloro-5,6,7,8-tetrahydroquinazolin-7-yl)methanol (reagent preparation 42, 0.80 g, 0.40 mmol), potassium carbonate (0.11 g, 0.81 mmol) and THF (15 mL) was added iodomethane (0.09 mL, 0.60 mmol). The reaction mixture was stirred for 18 hours and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by silica gel chromatography provided 4-chloro-7-(methoxymethyl)-5,6,7,8-tetrahydroquinazoline (0.03 g, 35% yield) as a waxy solid. MS (ES) for C10H13ClN2O: 213 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH2:13])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[CH2:25]([O:27][C:28]1[CH:33]=[CH:32][N:31]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[C:30](=[O:41])[C:29]=1[C:42](Cl)=[O:43])[CH3:26]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:15]([F:16])=[CH:14][C:12]([NH:13][C:42]([C:29]3[C:30](=[O:41])[N:31]([C:34]4[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=4)[CH:32]=[CH:33][C:28]=3[O:27][CH2:25][CH3:26])=[O:43])=[C:11]([F:17])[CH:10]=2)[CH:5]=[CH:4][N:3]=1
Reactant: CCOc1ccn(-c2ccc(F)cc2)c(=O)c1C(=O)Cl
Reactant: Nc1cc(F)c(Oc2ccnc(Cl)c2)cc1F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCOc1ccn(-c2ccc(F)cc2)c(=O)c1C(=O)Nc1cc(F)c(Oc2ccnc(Cl)c2)cc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.5 %

Procedure:
To a solution of Example A2 (29 g, 113 mmol) and triethylamine (23 g, 226 mmol) in THF (400 mL) was added freshly prepared 4-ethoxy-1-(4-fluoro-phenyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl chloride (33.5 g, 113 mmol) and the mixture was stirred at RT overnight. The mixture was concentrated in vacuo, and the residue was diluted with water (500 mL) and extracted with EtOAc (3×500 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated to afford N-(4-((2-chloropyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (51 g, 87% yield).
Reaction SMILES: C([O-])(O)=O.[Na+].[CH3:6][C@@H:7]([NH2:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=1[CH3:25])[C:19](Cl)=[O:20]>C(Cl)Cl>[C:8]1([C@H:7]([NH:14][C:19]([C:18]2[CH:22]=[CH:23][C:24]([CH3:25])=[C:16]([Br:15])[CH:17]=2)=[O:20])[CH3:6])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Cc1ccc(C(=O)Cl)cc1Br
Reactant: C[C@@H](N)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1ccc(C(=O)N[C@H](C)c2ccccc2)cc1Br
Temperature: 25 °C
Reaction time: 16 h
Yield: 96 %

Procedure:
To a 500 mL Erlenmeyer flask equipped with a stir bar was added 100 mL of sat. aq. NaHCO3 solution followed by 2.79 g of (R)-α-methylbenzylamine (0.023 mol) in 100 mL of CH2CH2. 3-Bromo-4-methylbenzoyl chloride in CH2Cl2 (from above) was added dropwise to the Erlenmeyer flask and the reaction mixture was continued to stir at RT for 16 hours. The organic phase was diluted with 50 mL of CH2CH2, separated from aqueous phase, dried over Na2SO4 and concentrated in vacuo. The residue was washed with 50 mL of Et2O and dried in an oven at 40 C overnight to afford light yellow solid (7.0 g, 0.022 mol, 96%).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]2[S:13][C:12]3[CH:14]=[C:15]([OH:19])[CH:16]=[C:17]([OH:18])[C:11]=3[CH2:10][CH2:9][C:8]=2[CH:20]=1)(=O)[CH3:2].Cl.[NH2:22][OH:23].C([O-])(=O)C.[Na+]>C(O)C.O>[OH:23][N:22]=[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[S:13][C:12]3[CH:14]=[C:15]([OH:19])[CH:16]=[C:17]([OH:18])[C:11]=3[CH2:10][CH2:9][C:8]=2[CH:20]=1)[CH3:2]
Reactant: NO
Reactant: CC(=O)c1ccc2c(c1)CCc1c(O)cc(O)cc1S2
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(=NO)c1ccc2c(c1)CCc1c(O)cc(O)cc1S2
Temperature: 120 °C
Reaction time: 3 h
Yield: 63.3 %

Procedure:
In ethanol, 180 mg of 8-acetyl-10,11-dihydrodibenzo[b,f]thiepin-1,3-diol (63) was dissolved, and an aqueous solution of 49 mg of hydroxylamine hydrochloride and 100 mg of sodium acetate dissolved in 1 mL of water was added thereto. The mixed solution was stirred at 120° C. for 3 hours, concentrated under reduced pressure and then, extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution and then, dried with anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent; hexane:ethyl acetate=1:1). Upon recrystallization from chloroform-hexane, 120 mg of skin-colored amorphous title compound was obtained (yield 63%). Melting Point: 215.4 to 217.5° C.
Reaction SMILES: [O:1]=[C:2]1[CH2:5][CH:4]([C:6](O)=O)[CH2:3]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:42][NH:43][C:44]1[C:45]([NH2:50])=[CH:46][CH:47]=[CH:48][CH:49]=1>C1COCC1>[CH3:42][N:43]1[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=2[N:50]=[C:6]1[CH:4]1[CH2:5][C:2](=[O:1])[CH2:3]1
Reactant: CNc1ccccc1N
Reactant: O=C1CC(C(=O)O)C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cn1c(C2CC(=O)C2)nc2ccccc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of 3-oxocyclobutanecarboxylic acid (0.5 g, 4.4 mmol) and DIPEA (2.2 mL, 13.2 mmol) in dry THF (10 mL) under N2 was added HATU (2.0 g, 5.3 mmol) and N′-methylbenzene-1,2-diamine (0.8 g, 6.6 mmol) in one portion. The reaction mixture was stirred at room temperature for 2 h and the solvent was removed under reduced pressure. AcOH (5 mL) was added and the mixture was stirred at room temperature for 2 h. The solvent was removed and the residue was partitioned between EtOAc and a 5% NaHCO3 aqueous solution. The aqueous layer was extracted with EtOAc (2×10 mL) and the combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (eluent: 1/1, Pet ether/EtOAc) to give Intermediate 1 as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.75-7.58 (m, 1H), 7.35-7.09 (m, 3H), 3.86-3.61 (m, 4H), 3.60-3.35 (m, 1H), 2.74 (s, 3H). MS: m/z=200.1 (M+).
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10](Br)[CH3:11]>>[C:1]1([CH:7]([CH2:10][CH3:11])[C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCBr
Reactant: N#CCc1ccccc1
Product: CCC(C#N)c1ccccc1
Yield: 98 %

Procedure:
Using the method of Procedure A.(a) 1, alkylation of phenylacetonitrile with ethyl bromide gave a 98% yield of the title compound, b.p. 110°-116° at 13 mm. (Lit.1 b.p. 124°-126° at 25 mm.).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:35])([C:29]2[N:30]([CH3:34])[CH:31]=[N:32][CH:33]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[NH:15][C:14](=[O:19])[CH:13]=[C:12]3[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:27][CH3:28])[CH:21]=2)=[CH:4][CH:3]=1.Br[CH2:37][CH:38]1[CH2:40][CH2:39]1>>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:35])([C:29]2[N:30]([CH3:34])[CH:31]=[N:32][CH:33]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH2:37][CH:38]2[CH2:40][CH2:39]2)[C:14](=[O:19])[CH:13]=[C:12]3[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH2:27][CH3:28])[CH:21]=2)=[CH:4][CH:3]=1
Reactant: CCOc1cccc(-c2cc(=O)[nH]c3ccc(C(O)(c4ccc(Cl)nc4)c4cncn4C)cc23)c1
Reactant: BrCC1CC1
Product: CCOc1cccc(-c2cc(=O)n(CC3CC3)c3ccc(C(O)(c4ccc(Cl)nc4)c4cncn4C)cc23)c1
Yield: 7.2 %

Procedure:
The same procedure described in example 8, 6-[(6-chloro-pyridin-3-yl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-ethoxy-phenyl)-1H-quinolin-2-one (50 mg, 0.103 mmol) and (bromomethyl)cyclopropane (0.020 ml, 0.206 mmol) generated the title compound as a white solid (4 mg, 7% yield).
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:11]([O:13][C:14]([C:16]1[CH:17]=[C:18]([CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:24](=[O:35])[CH2:23]2)[CH:19]=[CH:20][CH:21]=1)=[O:15])[CH3:12].[CH3:36]I>C1COCC1>[CH2:11]([O:13][C:14]([C:16]1[CH:17]=[C:18]([CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:24](=[O:35])[CH:23]2[CH3:36])[CH:19]=[CH:20][CH:21]=1)=[O:15])[CH3:12]
Reactant: CCOC(=O)c1cccc(C2CCN(C(=O)OC(C)(C)C)C(=O)C2)c1
Reactant: CI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cccc(C2CCN(C(=O)OC(C)(C)C)C(=O)C2C)c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
Potassium bis(trimethylsilyl)amide (14 g, 71 mmol) was mixed with 300 mL of THF in a 1000 mL flame-dried round bottomed flask and the resulting mixture was cooled to −78° C. tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-2-oxopiperidine-1-carboxylate (22.5 g, 64.8 mmol) dissolved in 150 mL of THF was added slowly to the mixture, via an addition funnel, and the resulting reaction mixture was stirred at −78° C. for 30 min. Methyl iodide (12.1 mL, 195 mmol) was then added dropwise and the reaction mixture was allowed to stir at −78° C. for 4 h before being allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride and extracted 3 times with ether. The combined ethereal layers were washed with brine and dried over MgSO4, filtered, and concentrated under reduced pressure. The product was purified by flash chromatography (10-20% EA/hexanes) to give 6.1 g of the trans racemate of tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3-methyl-2-oxopiperidine-1-carboxylate (26%).
Reaction SMILES: [CH2:1]([C:3]1[C:10]([NH2:11])=[CH:9][CH:8]=[CH:7][C:4]=1[O:5][CH3:6])[CH3:2].[OH:12][C:13]1C2C(=C(C)C(OC)=CC=2)N=[C:15]([C:26]2[S:27][CH:28]=[C:29]([CH:31]([CH3:33])[CH3:32])[N:30]=2)[CH:14]=1>>[CH2:1]([C:3]1[C:4]([O:5][CH3:6])=[CH:7][CH:8]=[C:9]2[C:10]=1[N:11]=[C:15]([C:26]1[S:27][CH:28]=[C:29]([CH:31]([CH3:32])[CH3:33])[N:30]=1)[CH:14]=[C:13]2[OH:12])[CH3:2]
Reactant: COc1ccc2c(O)cc(-c3nc(C(C)C)cs3)nc2c1C
Reactant: CCc1c(N)cccc1OC
Product: CCc1c(OC)ccc2c(O)cc(-c3nc(C(C)C)cs3)nc12

Procedure:
The title compound was prepared from 2-ethyl-m-anisidine (68) following the procedure (Steps 3-5) reported for the preparation of 4-hydroxy-2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinoline (36): m/z=329 (M+H)+.
Reaction SMILES: [S:1](Cl)(Cl)=[O:2].C[Si](C)(C)[N:7]([Si](C)(C)C)[C:8](=[O:31])[C:9]([F:30])([F:29])[C:10]([F:28])([F:27])[C:11]([F:26])([F:25])[C:12]([F:24])([F:23])[C:13]([F:22])([F:21])[C:14]([F:20])([F:19])[C:15]([F:18])([F:17])[F:16]>>[S:1](=[N:7][C:8](=[O:31])[C:9]([F:29])([F:30])[C:10]([F:27])([F:28])[C:11]([F:25])([F:26])[C:12]([F:23])([F:24])[C:13]([F:21])([F:22])[C:14]([F:20])([F:19])[C:15]([F:18])([F:17])[F:16])=[O:2]
Reactant: C[Si](C)(C)N(C(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)[Si](C)(C)C
Reactant: O=S(Cl)Cl
Product: O=S=NC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
Next, thionyl chloride (SOCl2) 2.4 g was added gradually to N,N-bis(trimethylsilyl)perfluorooctaneamide 12 g in the dry nitrogen atmosphere, which was allowed to react for two hours while being stirred. Then this was distilled and thereby sulfinylperfluorooctaneamide was obtained.
Reaction SMILES: [F:1][C:2]1[C:3]([B:12]2[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]2)=[CH:4][C:5]2[NH:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.C([O-])([O-])=O.[K+].[K+].N#N.[CH2:29](Br)[CH:30]=[CH2:31]>CN(C=O)C.O>[CH2:31]([N:10]1[CH2:9][CH2:8][O:7][C:6]2[CH:11]=[C:2]([F:1])[C:3]([B:12]3[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]3)=[CH:4][C:5]1=2)[CH:30]=[CH2:29]
Reactant: CC1(C)OB(c2cc3c(cc2F)OCCN3)OC1(C)C
Reactant: C=CCBr
Agent: N#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCN1CCOc2cc(F)c(B3OC(C)(C)C(C)(C)O3)cc21
Temperature: 70 °C
Yield: 74.8 %

Procedure:
A solution of 7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.503 g, 1.802 mmol, Ref. WO20100130034) and K2CO3 (0.504 g, 3.65 mmol) in dry DMF (5 mL) was sparged with N2 for 5 min, then treated with allyl bromide (0.8 mL, 9.17 mmol). The reaction tube was sealed then heated (70° C.) for 22 h. The reaction was diluted with water (50 mL) and extracted into EtOAc (50 mL). The organic layer was washed with water, brine, and then dried (Na2SO4), filtered, and concentrated. The residue was purified by biotage (4 g SiO2, 5% (3 CV), 5-40% (15 CV), 40% (2 CV), EtOAc in hexanes), affording the desired product (0.430 g, 1.347 mmol, 74.8% yield) as a clear viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.03 (6, J=5.7 Hz, 1H), 6.51 (d, J=9.9 Hz, 1H), 5.84-5.94 (m, 1H), 5.26-5.31 (m, 1H), 5.24 (m, 1H), 4.25-4.32 (m, 2H), 3.87 (m, 2H), 3.19-3.25 (m, 2H), 1.34 (s, 12H). LCMS (M+H)=319.7.