Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.[CH3:19][O:20][C:21]1[CH:30]=[CH:29][CH:28]=[CH:27][C:22]=1[O:23][CH2:24][CH2:25][NH2:26]>>[CH2:18]([N:26]([CH2:25][CH2:24][O:23][C:22]1[CH:27]=[CH:28][CH:29]=[CH:30][C:21]=1[O:20][CH3:19])[CH2:3][CH:2]([OH:1])[CH2:4][O:5][C:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1)[C:17]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: c1ccc2c(c1)[nH]c1cccc(OCC3CO3)c12
Reactant: COc1ccccc1OCCN
Product: COc1ccccc1OCCN(Cc1ccccc1)CC(O)COc1cccc2[nH]c3ccccc3c12

Procedure:
reaction of 4-oxiranylmethoxy-9H-carbazole with benzyl-[2-(2-methoxy-phenoxy]-ethylamine to give a 1-{benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amino}-3-(9H-carbazol-4-yloxy)propan-2-ol;
Reaction SMILES: [CH3:1][CH:2]1[CH2:14][C:5]2=[C:6]3[C:11](=[CH:12][CH:13]=[C:4]2[C:3]1=[O:15])[CH2:10][CH2:9][CH2:8][CH2:7]3.[Al+3].[Cl-].[Cl-].[Cl-].[Br:20]Br.O>C(Cl)Cl>[Br:20][C:12]1[CH:13]=[C:4]2[C:3](=[O:15])[CH:2]([CH3:1])[CH2:14][C:5]2=[C:6]2[C:11]=1[CH2:10][CH2:9][CH2:8][CH2:7]2
Reactant: BrBr
Reactant: CC1Cc2c(ccc3c2CCCC3)C1=O
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CC1Cc2c(cc(Br)c3c2CCCC3)C1=O
Reaction time: 1 h

Procedure:
In a three-necked round-bottom 500 ml flask equipped with a reflux condenser, dropping funnel with pressure-equalizing, and mechanical stirrer a solution of 55.0 g (0.275 mol) of 2-methyl-1,2,6,7,8,9-hexahydro-3H-cyclopenta[a]naphthalen-3-one in 50 ml of CH2Cl2 was added dropwise with vigorous stirring for 1 h at −10° C. to a suspension of 92 g (0.69 mol) of AlCl3 in 100 ml of CH2Cl2. This mixture was stirred additionally for 1 h at this temperature; then 14.2 ml (44.0 g, 0.275 mol) of bromine was added dropwise with vigorous stirring for 1 h. The resulting mixture was stirred for 2 h at −10° C. and then overnight at ambient temperature, and, then, it was poured on 1000 cm3 of cold water. The organic layer was separated, the aqueous layer was extracted with 3×200 ml of methyl-tert-butyl ether. The combined extract was washed with saturated aqueous Na2SO3 to eliminate bromine and with aqueous Na2CO3. It was then dried over K2CO3, and evaporated to dryness. Fractional distillation gave a yellowish liquid, b.p. 195-198° C./4 mm Hg. Yield 58.3 g (76%).
Reaction SMILES: C(N(CC)CC)C.[CH:8]([C:11]1[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:15]=[C:14]([CH:21]([CH3:23])[CH3:22])[C:12]=1[NH2:13])([CH3:10])[CH3:9].[Br:24][CH2:25][C:26](Br)=[O:27]>C(Cl)(Cl)Cl>[Br:24][CH2:25][C:26]([NH:13][C:12]1[C:11]([CH:8]([CH3:10])[CH3:9])=[CH:17][C:16]([CH:18]([CH3:20])[CH3:19])=[CH:15][C:14]=1[CH:21]([CH3:23])[CH3:22])=[O:27]
Reactant: O=C(Br)CBr
Reactant: CC(C)c1cc(C(C)C)c(N)c(C(C)C)c1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(C)c1cc(C(C)C)c(NC(=O)CBr)c(C(C)C)c1
Reaction time: 1 h
Yield: 80.8 %

Procedure:
Triethylamine (111 mg, 1.1 mmol) was added to a solution of 2,4,6-triisopropylaniline (219 mg, 1.0 mmol) in chloroform (3 ml), then bromoacetyl bromide (222 mg, 1.1 mmol) was gradually dropped thereinto with ice-cooling and the mixture was stirred for 1 hour. The reaction mixture was concentrated and the residue was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, an aqueous solution of sodium bicarbonate and a saturated sodium chloride solution successively and dried over magnesium sulfate and the solvent was evaporated therefrom. The residue was purified by a silica gel column chromatography (15 g of silica gel; developing solvent, hexane:acetone=5:1) followed by recrystallizing from hexane-ether to provide 275 mg (yield 81%) of 2-Bromo-N-(2,4,6-triisopropylphenyl)acetamide as colorless needles.
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][C@H:14]([N:17]([C:25](=[O:28])[CH2:26][CH3:27])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C@H:13]([CH3:29])[CH2:12]1)=O)C1C=CC=CC=1>CO.C(O)(=O)C.[Pd]>[CH3:29][C@H:13]1[C@@H:14]([N:17]([C:25](=[O:28])[CH2:26][CH3:27])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[CH2:15][CH2:16][NH:11][CH2:12]1
Reactant: CCC(=O)N(c1ccccc1F)[C@H]1CCN(C(=O)OCc2ccccc2)C[C@H]1C
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: CCC(=O)N(c1ccccc1F)[C@H]1CCNC[C@H]1C
Reaction time: 5 h

Procedure:
A mixture of cis-1-benzyloxycarbonyl-3-methyl-4-[(1-oxopropyl)-2-fluorophenylamino]-piperidine (576 mg, 1.45 mmol) and 10% Pd-C (100 mg) in methanol (25 ml) and acetic acid (5 ml) is hydrogenated at 50 psi for five hours. The reaction mixture is filtered through celite and the filtrate is concentrated. The residue is diluted with ethyl acetate, basified to pH 11 with 2N NaOH and shaken. The separated organics are dried over sodium sulfate and concentrated to give cis-3-methyl-4-[(1-oxopropyl)-2-fluorophenylamino]piperidine as an oil: 333 mg; 87%.
Reaction SMILES: O[C:2]1([C:26]2[C:35]([OH:36])=[CH:34][C:29]3[O:30][CH2:31][CH2:32][O:33][C:28]=3[CH:27]=2)[C:10]2[CH:9]=[C:8]3[O:11][CH2:12][CH2:13][O:14][C:7]3=[CH:6][C:5]=2[N:4]([CH2:15][C:16]2[O:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=2)[C:3]1=[O:25].OC1(C2C(O)=CC3OCCC=3C=2)C2C=C3OCCOC3=CC=2N(CC2OC(C(F)(F)F)=CC=2)C1=O>>[OH:36][C:35]1[C:26]([CH:2]2[C:10]3[CH:9]=[C:8]4[O:11][CH2:12][CH2:13][O:14][C:7]4=[CH:6][C:5]=3[N:4]([CH2:15][C:16]3[O:17][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:20]=3)[C:3]2=[O:25])=[CH:27][C:28]2[O:33][CH2:32][CH2:31][O:30][C:29]=2[CH:34]=1
Reactant: O=C1N(Cc2ccc(C(F)(F)F)o2)c2cc3c(cc2C1(O)c1cc2c(cc1O)OCCO2)OCCO3
Agent: O=C1N(Cc2ccc(C(F)(F)F)o2)c2cc3c(cc2C1(O)c1cc2c(cc1O)OCC2)OCCO3
Product: O=C1C(c2cc3c(cc2O)OCCO3)c2cc3c(cc2N1Cc1ccc(C(F)(F)F)o1)OCCO3

Procedure:
Following the procedure as described in PREPARATION 26C, and making non-critical variations using 8-hydroxy-8-(7-hydroxy-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-((5-(trifluoromethyl)furan-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxino[2,3-f]indol-7(3H)-one to replace 8-hydroxy-8-(6-hydroxy-2,3-dihydrobenzofuran-5-yl)-6-((5-(trifluoromethyl)furan-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxino[2,3-f]indol-7(3H)-one, 8-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-6-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3,6,8-tetrahydro-7H-[1,4]dioxino[2,3-f]indol-7-one was obtained (89%): 1H NMR (300 MHz, CDCl3) δ8.46 (s, 1H), 6.86 (s, 1H), 6.69 (d, J=2.9 Hz, 1H), 6.61 (s, 1H), 6.54 (s, 1H), 6.45 (s, 1H), 6.29 (d, J=2.9 Hz, 1H), 4.95 (s, 1H), 4.89-4.74 (m, 2H), 4.31-4.06 (m, 8H).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:32])[C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:26]=[CH:25][N:24]=[C:23]4[C:18]=3[C:19]3[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=3[C:21](=[O:27])[NH:22]4)=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.NC1C=CC=CC=1>>[O:27]=[C:21]1[C:20]2[CH:28]=[CH:29][CH:30]=[CH:31][C:19]=2[C:18]2[C:23](=[N:24][CH:25]=[CH:26][C:17]=2[NH:16][C:13]2[CH:14]=[CH:15][C:10]([C:9]([NH:8][C:5]3[CH:4]=[CH:3][CH:2]=[CH:7][CH:6]=3)=[O:32])=[CH:11][CH:12]=2)[NH:22]1
Reactant: O=C(Nc1ccc(F)cc1)c1ccc(Nc2ccnc3[nH]c(=O)c4ccccc4c23)cc1
Solvent: Nc1ccccc1
Product: O=C(Nc1ccccc1)c1ccc(Nc2ccnc3[nH]c(=O)c4ccccc4c23)cc1

Procedure:
The title compound was synthesized according to the procedure described for the preparation of Example 300 using the carboxylic acid intermediate from example 316 and aniline to provide 317. LC-MS (M+H=407, obsd.=407).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:24])[C:11]([C:17]1[CH:22]=[CH:21][N:20]=[C:19]([Cl:23])[CH:18]=1)([OH:16])[C:12]([F:15])([F:14])[F:13].[CH3:25][O:26][C:27]([C:29]1[CH:30]=[N:31][C:32](Cl)=[N:33][CH:34]=1)=[O:28]>>[CH3:25][O:26][C:27]([C:29]1[CH:30]=[N:31][C:32]([O:9][CH2:8][C:6]2[CH:5]=[CH:4][C:3]([CH:10]([CH3:24])[C:11]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([Cl:23])[CH:18]=3)([OH:16])[C:12]([F:15])([F:14])[F:13])=[C:2]([Cl:1])[CH:7]=2)=[N:33][CH:34]=1)=[O:28]
Reactant: CC(c1ccc(CO)cc1Cl)C(O)(c1ccnc(Cl)c1)C(F)(F)F
Reactant: COC(=O)c1cnc(Cl)nc1
Product: COC(=O)c1cnc(OCc2ccc(C(C)C(O)(c3ccnc(Cl)c3)C(F)(F)F)c(Cl)c2)nc1

Procedure:
The title compound was prepared in analogy to Example 93, step 7 from 3-(2-chloro-4-hydroxymethyl-phenyl)-2-(2-chloro-pyridin-4-yl)-1,1,1-trifluoro-butan-2-ol (obtained in Example 120, step 1) by alkylation with methyl-2-chloropyrimidine-5-carboxylate [CAS Reg. No. 287714-35-6]. MS (m/e)=516.1 [MH+].