Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN1CCOCC1.ClC(OCC(C)C)=O.[CH2:16]([O:23][C:24]1[CH:41]=[CH:40][C:39]2[C@@H:38]3[C@H:29]([C@H:30]4[C@@:34]([CH2:36][CH2:37]3)([CH3:35])[C@@H:33]([OH:42])[CH2:32][CH2:31]4)[C@H:28]([CH:43]=[CH:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][C:53](O)=[O:54])[CH2:27][C:26]=2[CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH3:56][NH:57][CH2:58][CH:59]([CH3:61])[CH3:60].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:58]([N:57]([CH3:56])[C:53](=[O:54])[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48][CH2:47][CH2:46][CH2:45][CH:44]=[CH:43][C@@H:28]1[CH2:27][C:26]2[CH:25]=[C:24]([O:23][CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:41]=[CH:40][C:39]=2[C@@H:38]2[C@@H:29]1[C@H:30]1[C@@:34]([CH2:36][CH2:37]2)([CH3:35])[C@@H:33]([OH:42])[CH2:32][CH2:31]1)[CH:59]([CH3:61])[CH3:60]
Reactant: C[C@]12CC[C@@H]3c4ccc(OCc5ccccc5)cc4C[C@@H](C=CCCCCCCCCC(=O)O)[C@H]3[C@@H]1CC[C@@H]2O
Reactant: CNCC(C)C
Agent: CC(C)COC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: CC(C)CN(C)C(=O)CCCCCCCCC=C[C@@H]1Cc2cc(OCc3ccccc3)ccc2[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
N-Methylmorpholine (0.028 ml.) and isobutyl chloroformate (0.038 ml.) were successively added to a stirred solution of 11-(3-benzyloxy-17β-hydroxyoestra-1,3,5(10)-trien-7α-yl)undec-10-enoic acid (0.109 g.) in tetrahydrofuran (3 ml.) which was cooled to -10° C. The mixture was stirred at -10° C. for 30 minutes, N-methylisobutylamine (0.05 ml.) was added and the mixture was stirred at laboratory temperature for 2 hours. Saturated aqueous sodium bicarbonate solution (5 ml.) was added and the mixture was extracted 3 times with methylene chloride (10 ml. each time). The combined extracts were washed with water (2 ml.), dried and evaporated to dryness, and there was thus obtained as oily residue N-isobutyl-N-methyl-11-(3-benzyloxy-17β-hydroxyoestra-1,3,5(10)-trien-7αyl)undec-10-enamide.
Reaction SMILES: Br[C:2]1[C:11]2[O:10][CH:9]([CH3:12])[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6][C:5]=2[S:4][CH:3]=1.[F:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:20][C:21]1[CH:26]=[C:25]([C:2]2[C:11]3[O:10][CH:9]([CH3:12])[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6][C:5]=3[S:4][CH:3]=2)[CH:24]=[CH:23][CH:22]=1
Reactant: CC1CN(C(=O)OC(C)(C)C)Cc2scc(Br)c2O1
Reactant: OB(O)c1cccc(F)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Product: CC1CN(C(=O)OC(C)(C)C)Cc2scc(-c3cccc(F)c3)c2O1
Temperature: 25 °C
Yield: 77.4 %

Procedure:
A mixed solution of tert-butyl 8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate (348 mg) obtained in Example 6, steps 1-6, (3-fluorophenyl)boronic acid (182 mg), dichlorobis(triphenylphosphine)palladium (35 mg) and potassium carbonate (415 mg) in DME-water (1:1, 10 ml) was stirred at 85° C. for 2 hr under a nitrogen stream. The reaction solution was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 5-12% ethyl acetate/hexane) to give the title compound (281 mg, 77%) as a colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7](=[O:13])[CH2:6][CH2:5]2.Cl[CH2:15][CH:16]1[CH2:20][O:19][C:18]([CH3:22])([CH3:21])[O:17]1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH3:21][C:18]1([CH3:22])[O:17][CH:16]([CH2:15][O:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][C:10]=2[O:11][CH3:12])[C:7](=[O:13])[CH2:6][CH2:5]3)[CH2:20][O:19]1
Reactant: COc1cc2c(cc1O)CCC2=O
Reactant: CC1(C)OCC(CCl)O1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2c(cc1OCC1COC(C)(C)O1)CCC2=O
Temperature: 95 °C
Reaction time: 72 h

Procedure:
A mixture of 5-Hydroxy-6-indan-1-one, Intermediate H, (0.50 g, 0.0028 mol), 4-chloromethyl-2,2-dimethyl-1,3-dioxolane (0.766 mL, 0.0056 mol), potassium carbonate (1.54 g, 0.011 mol) and DMF (20.0 mL) was stirred at 95° C. for 3 days. Water (150.0 mL) was added and the mixture was extracted with ethyl acetate (2×150 mL). The organic layer was washed with sat. NaHCO3, brine and dried over Na2SO4. The solvent was then removed in vacuo to yield 5-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6-methoxy-indan-1-one (Intermediate I) as light brown solid. MS m/z 293 (M+H)+.
Reaction SMILES: CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:44]1[N:45]=[CH:46][C:47]2[C:52]([CH:53]=1)=[CH:51][CH:50]=[CH:49][CH:48]=2.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:60][C:61]1[N:66]=[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])[C:64]([C:74]#[N:75])=[N:63][CH:62]=1>C1(C)C=CC=CC=1.CN(C=O)C.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].CCOCC>[C:74]([C:64]1[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])=[N:66][C:61]([NH:60][C:44]2[N:45]=[CH:46][C:47]3[C:52]([CH:53]=2)=[CH:51][CH:50]=[CH:49][CH:48]=3)=[CH:62][N:63]=1)#[N:75]
Reactant: Clc1cc2ccccc2cn1
Reactant: CCOC(=O)COc1nc(N)cnc1C#N
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CCOC(=O)COc1nc(Nc2cc3ccccc3cn2)cnc1C#N
Temperature: 100 °C
Reaction time: 0.25 h
Yield: 25 %

Procedure:
A mixture of tris(dibenzylideneacetone)dipalladium (0) (39 mg, 0.043 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (50 mg, 0.086 mmol) in toluene (1.5 mL) and DMF (1.5 mL) was degassed under a stream of nitrogen gas with stirring for 15 minutes. 3-Chloroisoquinoline (70 mg, 0.428 mmol), caesium carbonate (279 mg, 0.856 mmol) and ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate (105 mg, 0.471 mmol) were added and the mixture was degassed for a further 5 minutes. The mixture was then heated at 100° C. for 20 minutes, then at 130° C. for 20 minutes in a microwave reactor. The reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate. The aqueous phase was re-extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), passed sequentially through two PS-Thiol cartridges and concentrated to dryness. The residue was triturated with methanol and then ether affording ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate (37 mg, 0.107 mmol, 25%). LC-MS (2) Rt 2.89 min; m/z (ESI+) 350 (M+H).
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:17]=[CH:16][C:15]2[N:14]=[C:13]([NH2:18])[C:12]3[N:19]=[C:20]([CH2:25][O:26][CH3:27])[N:21]([CH2:22][CH2:23][CH3:24])[C:11]=3[C:10]=2[CH:9]=1.Br[CH2:29][CH2:30][CH2:31][Cl:32].CN(C)C=O>[Cl-].[Na+].O>[Cl:32][CH2:31][CH2:30][CH2:29][O:7][C:8]1[CH:17]=[CH:16][C:15]2[N:14]=[C:13]([NH2:18])[C:12]3[N:19]=[C:20]([CH2:25][O:26][CH3:27])[N:21]([CH2:22][CH2:23][CH3:24])[C:11]=3[C:10]=2[CH:9]=1
Reactant: CCCn1c(COC)nc2c(N)nc3ccc(O)cc3c21
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCn1c(COC)nc2c(N)nc3ccc(OCCCCl)cc3c21
Temperature: 50 °C
Reaction time: 8 h
Yield: 37.4 %

Procedure:
Cesium carbonate (5.7 g, 17.4 mmol, 2 eq) was added to a mixture of 8-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (2.5 g, 8.7 mmol, 1 eq), prepared as described in Examples 523-550 Parts A-D, 1-bromo-3-chloropropane (0.94 mL, 9.6 mmol, 1.1 eq), and 50 mL of N,N-dimethylformamide (DMF). The reaction mixture was stirred overnight. Analysis by HPLC indicated the reaction was incomplete. Additional cesium carbonate (2.85 g) was added to the reaction mixture and the mixture was heated to 50° C. overnight. Analysis by HPLC indicated the reaction was complete and the reaction mixture was poured into a brine solution (250 g of sodium chloride in 800 mL of deionized water). After 20 minutes, a dark brown/black material precipitated and was filtered The solid material was dissolved in chloroform, dried over magnesium sulfate, and purified by chromatography on a HORIZON HPFC system (eluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 30:70). The combined fractions were concentrated, dissolved in dichloromethane and methanol, and concentrated under reduced pressure to yield 1.18 g of 8-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]=[O:10])=[C:4]([CH:11]=[O:12])[CH:3]=1.Br[CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:9]=[O:10])=[C:4]([CH:11]=[O:12])[CH:3]=1
Reactant: O=CNc1ccc(Br)cc1C=O
Reactant: CCOC(=O)CCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)CCCN(C=O)c1ccc(Br)cc1C=O
Temperature: 70 °C
Reaction time: 24 h
Yield: 79.5 %

Procedure:
To 4-bromo-2-formylphenylformamide (18.07 g), ethyl 4-bromobutyrate (30.9 g) and potassium carbonate (21.9 g) was added DMF (160 ml), and the mixture was stirred at 70° C. for 24 hours. The mixture was dilute with ethyl acetate (1400 ml), washed with water (300 ml×3) and saturated brine (150 ml), and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (300 g, hexane:ethyl acetate=4:1→1:1) to give ethyl 4-(4-bromo-2,N-diformylanilino)butyrate (21.56 g, 80%).
Reaction SMILES: [Br:1][C:2]1[C:16]([CH3:17])=[CH:15][C:5]([O:6][CH:7]2[CH2:12][CH2:11][S:10](=[O:14])(=[O:13])[NH:9][CH2:8]2)=[CH:4][C:3]=1[CH3:18].[H-].[Na+].I[CH3:22]>CN(C)C=O>[Br:1][C:2]1[C:16]([CH3:17])=[CH:15][C:5]([O:6][CH:7]2[CH2:12][CH2:11][S:10](=[O:14])(=[O:13])[N:9]([CH3:22])[CH2:8]2)=[CH:4][C:3]=1[CH3:18]
Reactant: Cc1cc(OC2CCS(=O)(=O)NC2)cc(C)c1Br
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(OC2CCS(=O)(=O)N(C)C2)cc(C)c1Br
Temperature: 25 °C
Reaction time: 3 h

Procedure:
4-(4-Bromo-3,5-dimethyl-phenoxy)-[1,2]thiazinane 1,1-dioxide (110 mg) and sodium hydride (14.5 mg of a 60% mineral oil suspension) are suspended in 2 mL of N,N-dimethylformamide. Iodomethane (0.02 mL) is added and the reaction mixture is stirred at room temperature for 3 h. The solvent is removed, water is added and the reaction mixture is extracted with ethyl acetate. The organic phase is separated, dried over sodium sulfate and concentrated under vacuum. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 90:10→60:40) to give the title compound. Yield: 110 mg.
Reaction SMILES: C[C:2]([CH3:4])=[O:3].C1(C)C=CC=CC=1.[C:12]([O:15][CH:16]=[CH2:17])(=[O:14])[CH3:13].[C:18]1(=[O:24])[O:23][C:21](=[O:22])[CH:20]=[CH:19]1>C(O)C>[C:12]([O:15][CH:16]=[CH2:17])(=[O:14])[CH3:13].[C:18]([O:3][CH2:2][CH3:4])(=[O:24])/[CH:19]=[CH:20]\[C:21]([O-:23])=[O:22]
Reactant: O=C1C=CC(=O)O1
Reactant: CC(C)=O
Solvent: CCO
Solvent: C=COC(C)=O
Solvent: Cc1ccccc1
Product: CCOC(=O)/C=C\C(=O)[O-]

Procedure:
Part A above was repeated except that 535 ml of acetone were introduced into the kettle in place of 480 ml of toluene and the vinyl acetate/maleic anhydride polymerization was carried out at 53° C. instead of 63-65° C. Esterification of the VA/MA was achieved with 262 g of absolute ethanol by conducting the reaction at 70-75° C. for about 3 hours. The acetone was distilled off and the vinyl acetate/ethyl maleate (VA/EM) alternating copolymer was recovered as a solution of 44.18% copolymer solids in ethanol having a relative viscosity of 1.26, a specific viscosity of 0.26 and a K value of 31.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][NH:12][CH3:13])=[CH:8][C:6]=2[N:7]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH:26]=O>>[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][N:12]([CH3:13])[CH2:26][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=3)=[CH:8][C:6]=2[N:7]=1
Reactant: CNCc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: O=Cc1ccccn1
Product: CN(Cc1ccccn1)Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Yield: 71 %

Procedure:
(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine was reacted with pyridine-2-carbaldehyde using standard reductive amination conditions. The resulting crude solid was triturated with a small amount of diethyl ether to give (2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methyl-pyridin-2-ylmethyl-amine as a solid (71% yield), which was reacted with 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine according to General Procedure A. The resulting solid was triturated with diethyl ether and methanol to give 428 as a solid (93% yield). NMR (CDCl3, 400 MHz), 2.41 (3H, s), 3.84 (2H, s), 3.91 (4H, t, J=5.2), 3.94 (2H, s), 4.06 (4H, t, J=5.2), 5.24 (2H, s), 7.20-7.23 (1H, m), 7.32 (1H, s), 7.54 (1H, d, J=4.8), 7.70-7.74 (1H, m), 8.59-8.60 (1H, m), 9.30 (2H, s). MS: (ESI+): MH+=449
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7](O)=[O:8].[Cl-].[NH4+].Cl.C([N:21]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[NH2:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([NH2:21])=[O:8]
Reactant: CCN=C=NCCCN(C)C
Reactant: Nc1sc(-c2ccncc2)cc1C(=O)O
Agent: Cl
Agent: On1nnc2ccccc21
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: NC(=O)c1cc(-c2ccncc2)sc1N
Temperature: 25 °C
Reaction time: 8 h
Yield: 50.2 %

Procedure:
To a solution of 2-amino-5-(pyridin-4-yl)thiophene-3-carboxylic acid (2.20 g, 10 mmol), ammonium chloride (1.09 g, 20 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.30 g, 30 mmol) and 1-hydroxybenzotriazole (1800 mg, 12 mmol) in DMF (100 mL) was added triethylamine (3.0 g, 30 mmol) at room temperature. The reaction mixture was stirred overnight at room temperature. After removal of the solvent, the residue was purified by column chromatography on silica gel (MeOH: DCM=1:19) to give the title compound (1100 mg, 50%) as a brown solid:
Reaction SMILES: [F:1][C:2]1([F:32])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([C:19]([N:21]2[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]2)=[O:20])=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[Cl:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][N:35]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:33][C:34]1[N:35]=[CH:36][C:37]([N:11]2[C:12]3[C:17](=[CH:16][C:15]([C:19]([N:21]4[CH2:22][CH2:23][CH:24]([N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[CH2:25][CH2:26]4)=[O:20])=[CH:14][CH:13]=3)[CH:18]=[C:10]2[C:8]([N:5]2[CH2:6][CH2:7][C:2]([F:1])([F:32])[CH2:3][CH2:4]2)=[O:9])=[CH:38][CH:39]=1
Reactant: O=C(c1ccc2[nH]c(C(=O)N3CCC(F)(F)CC3)cc2c1)N1CCC(N2CCCC2)CC1
Reactant: OB(O)c1ccc(Cl)nc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(c1ccc2c(c1)cc(C(=O)N1CCC(F)(F)CC1)n2-c1ccc(Cl)nc1)N1CCC(N2CCCC2)CC1
Yield: 57 %

Procedure:
The title compound was synthesized in analogy to example 66, from (4,4-difluoro-piperidin-1-yl)-[5-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-1H-indol-2-yl]-methanone (example 169), 2-chloropyridine-5-boronic acid, copper(II) acetate and pyridine in dichloromethane, to give the desired product as a brown oil (57%).
Reaction SMILES: Cl[Si](C)(C)C.[BH4-].[Li+].[CH3:8][C:9]([CH3:36])([P:33](=[O:35])=[O:34])[N:10]([C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([O:29][CH2:30][C:31]#[N:32])[CH:23]=1)[S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21])(=[O:13])=[O:12].O>O1CCCC1>[CH3:8][C:9]([CH3:36])([P:33](=[O:35])=[O:34])[N:10]([C:22]1[CH:27]=[C:26]([CH3:28])[CH:25]=[C:24]([O:29][CH2:30][CH2:31][NH2:32])[CH:23]=1)[S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21])(=[O:12])=[O:13]
Reactant: COc1ccccc1S(=O)(=O)N(c1cc(C)cc(OCC#N)c1)C(C)(C)P(=O)=O
Agent: C[Si](C)(C)Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccccc1S(=O)(=O)N(c1cc(C)cc(OCCN)c1)C(C)(C)P(=O)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.9 %

Procedure:
3.3 ml Chlorotrimethylsilane was added dropwise under nitrogen and while cooling on ice to 0.29 g (13.2 mmol) lithium borohydride in 5 ml tetrahydrofuran, it was stirred for 1 h at room temperature, a solution of 0.93 g (2.2 mmol) N-(dimethyloxophosphinyl-methyl)-N-(3-cyanomethoxy-5-methyl-phenyl)-2-methoxy-benzenesulfonamide in 5 ml tetrahydrofuran was added dropwise, it was stirred for 1 h at room temperature, water was added dropwise, the solvent was removed in a vacuum, it was taken up in a small amount of dichloromethane and filtered over silica gel (dichloromethane:methanol=9:1), the solvent was removed in a vacuum and 900 mg (91%) N-(dimethyloxophosphinyl-methyl)-N-[3-(2-amino-ethoxy)-5-methyl-phenyl]-2-methoxy-benzenesulfonamide was obtained as an oil. MS (m/e)=426.
Reaction SMILES: [CH2:1]([NH:5][CH3:6])[CH2:2][CH2:3][CH3:4].[CH:7]1([N:13]=[C:14]=[N:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1>>[CH2:1]([N:5]([CH3:6])[C:14]([NH:13][CH:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1)=[N:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:2][CH2:3][CH3:4]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CCCCNC
Product: CCCCN(C)C(=NC1CCCCC1)NC1CCCCC1
Yield: 99.7 %

Procedure:
A mixture of 17.78 g of N-butyl-N-methylamine (0.204 mol) and of 21.05 g of dicyclohexylcarbodiimide (0.102 mol) is refluxed for 3 h. The GC analysis then shows a conversion of greater than 99.5% of the dicyclohexylcarbodiimide. The colorless final mixture is concentrated at 60° C. under 1 mbar for 2 h, to give 29.9 g of a colorless and virtually odorless liquid of medium viscosity, corresponding to the expected guanidine (yield 99.7%).
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:17])([CH2:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:18])[C:3]=1C(OCC)=O.Cl>O1CCOCC1>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH3:17])([CH2:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:4](=[O:18])[CH:3]=1
Reactant: CCOC(=O)C1=C(O)c2ccccc2C(C)(CCC(C)C)C1=O
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)CCC1(C)C(=O)C=C(O)c2ccccc21
Temperature: 25 °C
Yield: 65.9 %

Procedure:
A solution of Example 28D (2.06 g, 6.52 mmol) in 1,4-dioxane (25 mL) was treated with aqueous 1N hydrochloric acid solution (25 mL) and refluxed for 3 hours. The mixture was cooled to 25° C. and partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water and brine, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was triturated in hot hexane and filtered. The precipitate was dried to give the title compound (1.05 g, 66%). 1H NMR (300 MHz, CDCl3) δ ppm 0.44 (m, 0.5 H) 0.73 (m, 3.5 H) 0.80 (m, 3 H) 1.06 (m, 1 H) 1.39 (m, 1 H) 1.56 (s, 1.5 H) 1.59 (s, 1.5 H) 2.04 (m, 1 H) 2.30 (m, 1 H) 3.74 (s, 0.5 H) 3.75 (s, 0.5 H) 6.63 (s, 0.5 H) 7.46 (m, 2 H) 7.66 (m, 1 H) 8.08 (m, 0.5 H) 8.20 (m, 0.5 H). MS (DCI NH3+) m/z 262 (M+NH4)+.
Reaction SMILES: [CH3:1][C:2]1[C:10]2[C:9]([C:11]([C:13]3[NH:17][C:16]4[CH:18]=[CH:19][C:20]([C:22]#[N:23])=[CH:21][C:15]=4[N:14]=3)=[O:12])=[C:8]([CH3:24])[CH:7]=[C:6]([CH3:25])[C:5]=2[NH:4][CH:3]=1.[Li+].[BH4-].C1COCC1>>[OH:12][CH:11]([C:9]1[C:8]([CH3:24])=[CH:7][C:6]([CH3:25])=[C:5]2[C:10]=1[C:2]([CH3:1])=[CH:3][NH:4]2)[C:13]1[NH:17][C:16]2[CH:18]=[CH:19][C:20]([C:22]#[N:23])=[CH:21][C:15]=2[N:14]=1
Reactant: Cc1cc(C)c2[nH]cc(C)c2c1C(=O)c1nc2cc(C#N)ccc2[nH]1
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1cc(C)c2[nH]cc(C)c2c1C(O)c1nc2cc(C#N)ccc2[nH]1
Temperature: 25 °C

Procedure:
A solution of 2-(3,5,7-trimethyl-1H-indole-4-carbonyl)-1H-benzo[d]imidazole-5-carbonitrile (20 mg, 0.061 mmol) and LiBH4 in THF (2M, 2 mL, 4.00 mmol) was stirred at 50° C. for 2 h. The reaction mixture was cooled to room temperature. The mixture was quenched by half satd. aq. KHSO4 and basified by 5% NaHCO3. The layers were separated and the aqueous layer was extracted with CH2Cl2/2,2,2-trifluoroethanol (c.a. 9/1). The organic phase was washed with H2O and brine, dried over Na2SO4, and filtered. After concentration of the filtrate the resulting residue was purified by RP-HPLC (HC-A) to give the title compound. 1H NMR (400 MHz, ACETONITRILE-d3 with about 5 μL TFA) δ ppm 9.10 (br. s., 1H), 8.08 (s, 1H), 7.73-7.82 (m, 2H), 7.06 (s, 1H), 6.96 (s, 1H), 6.84 (s, 1H), 2.45 (s, 3H), 2.21 (br. s., 3H), 2.19 (s, 3H). HRMS calcd. for C20H18N4O (M+H)+ 331.1554. found 331.1555.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@:33]2([CH3:34])[C:9](=[CH:10][CH2:11][C@@H:12]3[C@@H:32]2[CH2:31][CH2:30][C@@:29]2([CH3:35])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:28])[CH2:18][CH2:19][CH:20]([O:24][C:25](=[O:27])[CH3:26])[CH:21]([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:36][C:37](=[O:39])[CH3:38])[CH2:6]1)(=[O:3])[CH3:2].BrN1C(C)(C)C(=O)N(Br)C1=O.COP(OC)OC.O[C@@H]1[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@@]2(C)[C@H]3CC[C@@H]2[C@H](C)CCC(OC(=O)C2C=CC=CC=2)C(C)C)C[C@@H](OC(=O)C2C=CC=CC=2)C1>C1(C)C(C)=CC=CC=1.CCCCCC>[C:1]([O:4][C@@H:5]1[C@@:33]2([CH3:34])[C:9](=[CH:10][CH:11]=[C:12]3[C@@H:32]2[CH2:31][CH2:30][C@@:29]2([CH3:35])[C@H:13]3[CH2:14][CH2:15][C@@H:16]2[C@H:17]([CH3:28])[CH2:18][CH2:19][CH:20]([O:24][C:25](=[O:27])[CH3:26])[CH:21]([CH3:23])[CH3:22])[CH2:8][C@@H:7]([O:36][C:37](=[O:39])[CH3:38])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC(CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C)C(C)C
Agent: CC(C)C(CC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(=O)c5ccccc5)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C)OC(=O)c1ccccc1
Agent: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: COP(OC)OC
Solvent: Cc1ccccc1C
Solvent: CCCCCC
Product: CC(=O)OC(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C)C(C)C
Reaction time: 1.5 h

Procedure:
150 mg of 1α,3β,24-triacetoxycholest-5-ene was reacted with 45 mg of 1,3-dibromo-5,5-dimethylhydantoine in 3 ml. of n-hexane for 15 minutes under reflux. The reaction mixture was cooled, and the resulting crystals were removed by filtration. The filtrate was concentrated at reduced pressure to afford a yellow oily substance. To this substance was added 1.3 ml. of xylene. The resulting solution was added dropwise over the course of about 15 minutes to a solution of 0.25 ml. of trimethylphosphite in 4 ml. of xylene under reflux, and the reaction was performed for an additional 90 minutes. The reaction mixture was then concentrated at a temperature of less than 75° C. to afford 148 mg of an oily substance. This substance was treated in the same way as in Example 5, (B). The final product showed the same UV, mass, and NMR spectrum data as the 1α,3β,24-triacetoxycholesta-5,7-diene obtained in Example 5, (B).
Reaction SMILES: [CH:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:10]=3[N:9]=[C:8]2[C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[N:25]=C(C2C=CC=CC=2)C(C2C=CC=CC=2)=[N:22]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:41][O:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]([C:51]([C:53]2[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=2)=O)=O)=[CH:45][CH:44]=1>>[CH3:41][O:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[C:51]([C:53]3[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][CH:54]=3)=[N:22][C:21]3[C:26](=[CH:27][CH:28]=[C:19]([C:8]4[N:7]([CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]5)[C:11]5[CH:12]=[CH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:10]=5[N:9]=4)[CH:20]=3)[N:25]=2)=[CH:45][CH:44]=1
Reactant: COc1ccc(C(=O)C(=O)c2ccc(OC)cc2)cc1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4ccccc4)c(-c4ccccc4)nc3c1)n2C1CCCCC1
Product: COc1ccc(-c2nc3ccc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)cc3nc2-c2ccc(OC)cc2)cc1

Procedure:
Prepared as described for Compound 406 using 4,4′-dimethoxybenzil in place of benzil.