Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:24]=[CH:23][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[O:7])=[CH:4][N:3]=1.[CH:25]1([NH:28][C:29](=[O:46])[C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:31]=2)[CH2:27][CH2:26]1>>[CH:25]1([NH:28][C:29]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[C:32]([C:2]3[CH:24]=[CH:23][C:5]([C:6]([NH:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[CH2:15][N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[O:7])=[CH:4][N:3]=3)[CH:31]=2)=[O:46])[CH2:26][CH2:27]1
Reactant: CN1CCN(Cc2ccccc2NC(=O)c2ccc(Cl)nc2)CC1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1B1OC(C)(C)C(C)(C)O1
Product: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc(C(=O)Nc2ccccc2CN2CCN(C)CC2)cn1

Procedure:
6-(5-Cyclopropylcarbamoyl-2-methyl-phenyl)-N-[2-(4-methylpiperazin-1-ylmethyl)phenyl]-nicotinamide was prepared from 6-chloro-N-[2-(4-methylpiperazin-1-ylmethyl)phenyl]nicotinamide (Intermediate 5) and N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (Intermediate 8) using General Method B. LCMS: retention time 2.36 min, MH+ 484. NMR: δH [2H6]-DMSO 11.70,(1H, b), 9.23,(1H, s), 8.50,(1H, d), 8.38,(1H, d), 8.33,(1H, d), 7.92, (1H, s), 7.83,(2H, m), 7.43,(1H, d), 7.36,(1H, t), 7.29,(1H, d), 7.11,(1H, t), 3.77,(2H, s), 2.87,(1H, m), 2.67-2.24,(1H, m), 2.13,(3H, s), 0.70,(2H, m), 0.58,(2H, m).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH:7]=[CH2:8])[CH:2]1[O:4][CH2:3]1.C([O-])([O-])=[O:10].[Na+].[Na+]>O>[CH2:6]([O:5][CH2:1][CH:2]([OH:4])[CH2:3][OH:10])[CH:7]=[CH2:8]
Reactant: O=C([O-])[O-]
Reactant: C=CCOCC1CO1
Agent: [Na+]
Solvent: O
Product: C=CCOCC(O)CO
Temperature: 80 °C
Reaction time: 12 h
Yield: 86 %

Procedure:
A 5,000 mL, 3-necked flask fitted with a mechanical stirrer, thermometer and 500 mL addition funnel was charged with water (2,000 mL) and 70% aqueous HClO4 (2.0 mL), then heated to 80° C. Allyl glycidyl ether (500 g, 4.38 mol) was added in one portion and the reaction mixture stirred for 12 hours. The mixture was neutralized by addition of 5% aqueous Na2CO3 to pH=8. The water was evaporated in vacuo to leave 550 g of crude product, which was distilled to yield 498 g (86%) of pure 3-allyloxy-1,2-propanediol: bp 76°-83° C. (0.4 mm).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20]Br)=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1.[CH2:22]([NH:24][CH2:25][CH2:26][OH:27])[CH3:23]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][N:24]([CH2:22][CH3:23])[CH2:25][CH2:26][OH:27])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: BrCCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1
Reactant: CCNCCO
Product: CCN(CCO)CCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1

Procedure:
According to the method in example 4, 3-(4-Bromo-phenyl)-6-(3-bromo-propoxy)-benzo[d]isothiazole and 2-(ethylamino)ethanol were converted to yield 2-[[3-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-propyl]-ethyl-amino]-ethanol, MS: 436 (MH+, 1Br).
Reaction SMILES: Cl[C:2]#[C:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[H-].[CH3:11][Al](C)C.[Na+].[Cl:16]/[CH:17]=[CH:18]/[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].Cl/C=C\CCCCCC.C#CCCCCCC>COCCOCCOC>[CH3:9]/[CH:8]=[CH:7]\[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:11].[Cl:16]/[CH:17]=[CH:18]/[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCC#CCl
Reactant: C[Al](C)C
Agent: C#CCCCCCC
Agent: CCCCCC/C=C/Cl
Agent: CCCCCC/C=C\Cl
Solvent: COCCOCCOC
Product: C/C=C\CCCCCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 17 %

Procedure:
Addition of 1-chloro-1-octyne to 1.5 equivalents of sodium trimethylaluminum hydride in diglyme at 0° C. with stirring for one hour resulted in the regio- and stereoselective formation of the E-alpha-chloroalkenylalanate, [HexHC=C(Cl)AlMe3 ]-Na+, in 89% yield as evidenced from 1H-NMR (the vinylic proton was present as a triplet, J=8 Hz, at 5.88 ppm) and gas chromatography (GC) analysis of the trans-1-chloro-1-octene obtained upon protonolysis. None of the corresponding cis-1-chloro-1-octene was observed by a gas chromatography comparison with an authentic sample. In addition, 11% of 1-octyne was found by gas chromatography. Allowing the reaction mixture to warm to room temperature and stirring for two hours produced by gas chromatography analysis cis-2-nonene (17%) with no trans-1-chloro-1-octene remaining. Hence, the migratory insertion reaction of the foregoing alpha-chloroalkenylalanate to form the vinylalane, HexHC=C(Me)AlMe2, did occur.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24]Br)=[C:20]([F:26])[CH:19]=2)=[O:17])[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:28][C:29]1([CH3:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:32]3[CH2:33][CH2:34][C:29]([OH:28])([CH3:35])[CH2:30][CH2:31]3)=[C:20]([F:26])[CH:19]=2)=[O:17])[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cn1ccc(OCc2ccccc2)cc1=O)c1ccc(CBr)c(F)c1
Reactant: CC1(O)CCNCC1
Product: CC1(O)CCN(Cc2ccc(C(=O)Cn3ccc(OCc4ccccc4)cc3=O)cc2F)CC1

Procedure:
4-Benzyloxy-1-{2-[3-fluoro-4-(4-hydroxy-4-methyl-piperidin-1-ylmethyl)-phenyl]-2-oxo-ethyl}-1H-pyridin-2-one is prepared as example 1.1b from 105 mg (0.24 mmol) 4-benzyloxy-1-[2-(4-bromomethyl-3-fluoro-phenyl)-2-oxo-ethyl]-1H-pyridin-2-one (preparation 16 h) and 84 mg (0.73 mmol) 4-hydroxy-4 methyl-piperidine.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[CH3:25])[CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH3:12])=[O:5].[H-].[Na+].[CH3:28]I.O>CN1CCCC1=O>[Cl:1][C:2]1[CH:16]=[C:15]([N:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[CH3:25])[CH3:28])[CH:14]=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH3:12])=[O:5]
Reactant: Cc1cc(F)ccc1Nc1ccc(C(=O)c2ccccc2C)c(Cl)c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1ccccc1C(=O)c1ccc(N(C)c2ccc(F)cc2C)cc1Cl
Reaction time: 18 h

Procedure:
A solution of 2-chloro-4-(4-fluoro-2-methyl-phenylamino)-2′-methylbenzophenone (Compound 116)(105 mg) in N-methyl-2-pyrolidinone (2.0 ml) was added sodium hydride (14 mg) in one portion under stirring. After 10 min at 0° C. methyl iodide (47 mg ) was added and the reaction mixture was stirred for 4 hours at room temperature followed by 18 hours at 100° C. The reaction mixture was poured into water and extracted with EtOAc. The organic phases were separated, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography using a mixture of diethylether/pentane 1:4 as eluant to yield the title compound.
Reaction SMILES: C[O:2][C:3]1[CH2:4][C:5]2[CH2:6][CH2:7][C@@H:8]3[C@@H:17]([C:18]=2[CH2:19][CH:20]=1)[CH2:16][CH2:15][C@@:13]1([CH3:14])[C@H:9]3[CH2:10][C@H:11]2[CH2:21][C@:12]21[O:22][CH3:23].S(=O)(=O)(O)O.O>CC(C)=O>[CH3:23][O:22][C@@:12]12[CH2:21][C@@H:11]1[CH2:10][C@H:9]1[C@H:8]3[C@H:17]([CH2:16][CH2:15][C@:13]21[CH3:14])[C:18]1[CH2:19][CH2:20][C:3](=[O:2])[CH2:4][C:5]=1[CH2:6][CH2:7]3
Reactant: COC1=CCC2=C(CC[C@@H]3[C@@H]2CC[C@@]2(C)[C@H]3C[C@H]3C[C@]32OC)C1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)=O
Product: CO[C@@]12C[C@@H]1C[C@H]1[C@@H]3CCC4=C(CCC(=O)C4)[C@H]3CC[C@@]12C
Temperature: 25 °C

Procedure:
10 g of 3,17-dimethoxy-16alpha,17alpha-methylene-estra-2,5(10)-diene is suspended in 165 ml of 80% aqueous acetone and is mixed with vigorous stirring with 0.2 ml of 25% sulfuric acid. Then, with stirring, it is heated on the water bath (60° C.) until all the steroid has gone into solution (about 30 minutes). Then, it is allowed to cool to room temperature and stirred one more hour. After the reaction has been completed, the steroid is precipitated by the addition of water, separated and dried. 9.5 g of crystalline 16alpha,17alpha-methylene compound, which was used in the next step without recrystallization, is obtained.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][OH:12])=[CH:7][C:6]=1[NH:13][C:14](=[O:32])[CH2:15][CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[O:30][CH3:31])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])([CH3:4])([CH3:3])[CH3:2].ClS([N:37]=[C:38]=[O:39])(=O)=O.C(OCC)(=O)C.CCCCCC>O1CCCC1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][O:12][C:38](=[O:39])[NH2:37])=[CH:7][C:6]=1[NH:13][C:14](=[O:32])[CH2:15][CH:16]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[O:30][CH3:31])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])([CH3:2])([CH3:3])[CH3:4]
Reactant: O=C=NS(=O)(=O)Cl
Reactant: CCCCCC(CC(=O)Nc1cc(CO)ccc1C(C)(C)C)c1ccc(OC)cc1OC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCCCC(CC(=O)Nc1cc(COC(N)=O)ccc1C(C)(C)C)c1ccc(OC)cc1OC
Reaction time: 2.5 h
Yield: 59 %

Procedure:
A solution of 401 mg (0.91 mmol) of N-[2-t-butyl-5-(hydroxymethyl)phenyl]-3-(2,4-dimethoxyphenyl)octanamide (prepared as described in Preparation 9) in 4 ml of tetrahydrofuran was cooled to -40° C. in a dry ice-acetonitrile bath. 102 μl (1.17 mmol) of chlorosulfonyl isocyanate were added to the cooled solution, and the resulting mixture was stirred for 2.5 hours. At the end of this time, the reaction was quenched by the addition of a phosphate buffer solution (pH 6.9), and the mixture was then extracted with ethyl acetate. The extract was washed with water and then with a saturated aqueous solution of sodium chloride, after which it was dried. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 30 g of silica gel, using a gradient elution method, with mixtures ethyl acetate of and hexane ranging from 2:1 to 3:1 by volume as the eluent, to give 260 mg (yield 59%) of the title compound as a foam-like substance.
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[CH2:4]O.C(Br)(Br)(Br)[Br:12].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[CH3:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[CH2:4][Br:12]
Reactant: Cc1ccc(CO)c(C)c1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Cc1ccc(CBr)c(C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.7 %

Procedure:
A solution of benzyl alcohol 9 (18.4 g; 135 mmol) and carbon tetrabromide (55.96 g; 169 mmol) in methylene chloride (220 ml) was cooled to 0° C. and treated in dropwise fashion with triphenylphosphine (44.33 g; 169 mmol) in 100 ml of methylene chloride. After the addition was complete the mixture was stirred overnight at room temperature. It was poured into ice-water and partitioned between methylene chloride and water. The organic phase was dried (MgSO4) and concentrated in vacuo. Chromatography of the residue, eluting with 10% ethyl acetate in hexane, gave 26 g (99%) of the product as a yellow liquid. 1HNMR (CDCl3): δ2.31, 2.38 (s, 3H each); 4.51 (s, 2H); 6.99 (m, 2H); 7.18 (d, 1H). IR (neat): 3013, 2972, 2921, 1617, 1507, 1450, 1262, 823 cm-1.
Reaction SMILES: O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([CH:47]=[CH:48][CH:49]=2)[C:43]([O:45]C)=O)=[N:8]1.O.[OH-].[Li+].[CH:53]1([CH2:56][NH2:57])[CH2:55][CH2:54]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>O1CCCC1.O1CCCC1.O>[NH:17]1[C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([C:43]([NH:57][CH2:56][CH:53]3[CH2:55][CH2:54]3)=[O:45])[CH:47]=[CH:48][CH:49]=2)=[N:20][CH:19]=[N:18]1
Reactant: COC(=O)c1cccc(-c2nn(C3CCCCO3)c3ccc(-c4ncn(C(c5ccccc5)(c5ccccc5)c5ccccc5)n4)cc23)c1
Reactant: NCC1CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: C1CCOC1
Product: O=C(NCC1CC1)c1cccc(-c2n[nH]c3ccc(-c4ncn[nH]4)cc23)c1
Temperature: 60 °C
Reaction time: 67 h
Yield: 100.8 %

Procedure:
To a stirred solution of methyl 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl) (1,2,4-triazol-3-yl)]-1H-indazol-3-yl}benzoate (0.431 g, 0.667 mmol) in a tetrahydrofuran/water mixture (2.70 mL/1.62 mL) was added lithium hydroxide monohydrate (0.0840 g, 2.00 mmol) and the mixture heated at 60° C. for 21 h. To this mixture was added tetrahydrofuran (2.00 mL), cyclopropylmethyl amine (0.161 mL, 1.86 mmol), 1-hydroxybenzotriazole hydrate (0.251 g, 1.86 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.356 g, 1.86 mmol). This reaction mixture was stirred for 67 h at ambient temperature. The mixture was extracted with ethyl acetate (2×). The combined organic extracts were washed with an aqueous saturated solution of sodium bicarbonate, followed by brine, dried over anhydrous sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography with 40–100% ethyl acetate/hexanes gave the title compound (0.241 g, 53% yield). ES-MS (m/z) 443 [M+1(−Tr)]+
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:17][C@@H:18]2[CH2:23][CH2:22][C@H:21]([C:24]([NH:26][CH:27]([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:4][C:5]([NH:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:6][CH:7]=1.[F:30][C:31]1[CH:65]=[CH:64][C:34]([C:35](/[N:37]=[C:38]2/N([C@H]3CC[C@@H](C(=O)NC(C)C)CC3)C3C=C(OCCOC)N=CC=3N/2)=[O:36])=[CH:33][CH:32]=1>>[F:30][C:31]1[CH:32]=[CH:33][C:34]([C:35](/[N:37]=[C:38]2/[N:17]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([C:24](=[O:25])[NH:26][CH:27]([CH3:29])[CH3:28])[CH2:20][CH2:19]3)[C:3]3[CH:4]=[C:5]([NH:8][CH2:9][CH2:10][N:11]4[CH2:16][CH2:15][O:14][CH2:13][CH2:12]4)[N:6]=[CH:7][C:2]=3[NH:1]/2)=[O:36])=[CH:64][CH:65]=1
Reactant: CC(C)NC(=O)[C@H]1CC[C@@H](Nc2cc(NCCN3CCOCC3)ncc2N)CC1
Reactant: COCCOc1cc2c(cn1)[nH]/c(=N\C(=O)c1ccc(F)cc1)n2[C@H]1CC[C@@H](C(=O)NC(C)C)CC1
Product: CC(C)NC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccc(F)cc3)[nH]c3cnc(NCCN4CCOCC4)cc32)CC1

Procedure:
The title compound was prepared from cis-4-(5-amino-2-(2-morpholinoethylamino)pyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide using a procedure analogous to that used to prepare (E)-4-fluoro-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(2-methoxyethoxy)-1H-imidazo[4,5-c]pyridin-2(3H)-ylidene)benzamide. Isolated as an off-white solid (23 mg, 23% yield). M/Z calc'd for C29H38FN7O3: 551.66. found 552 [M+H].
Reaction SMILES: CO[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:23]([NH:24][CH:25]([CH3:27])[CH3:26])=[CH:22][CH:21]=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[O:11])=[CH:6][CH:5]=1.[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32][NH2:33]>>[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32][NH:33][C:3]([C:4]1[CH:5]=[CH:6][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[C:23]([NH:24][CH:25]([CH3:27])[CH3:26])=[CH:22][CH:21]=[CH:20][N:19]=3)[CH2:14][CH2:13]2)=[O:11])=[CH:8][CH:9]=1)=[O:28]
Reactant: COC(=O)c1ccc(C(=O)N2CCN(c3ncccc3NC(C)C)CC2)cc1
Reactant: CN(C)CCN
Product: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)NCCN(C)C)cc2)CC1
Yield: 79 %

Procedure:
By the same procedure as described in the example 45, synthesis was carried out starting with 4-[1-[3-(isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]benzoic acid methyl ester and using N,N-dimethylethylenediamine. Then, the product was recrystallized using ethanol and isopropyl ether to give the desired compound.
Reaction SMILES: FC1C=CC(CCN2CCC([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH3:24])[CH:21]=4)[CH:16]=[CH:15]3)CC2)=CC=1.O>FC(F)(F)C(O)=O>[CH3:24][O:23][C:20]1[CH:21]=[C:22]2[C:17]([CH2:16][CH2:15][NH:14]2)=[CH:18][CH:19]=1
Reactant: COc1ccc2ccn(C3CCN(CCc4ccc(F)cc4)CC3)c2c1
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2c(c1)NCC2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 98.4 %

Procedure:
A 1 M solution (0.18 ml) of a borane/tetrahydrofuran complex was added dropwise at 0° C. into a solution of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-methoxyindole (24 mg) in trifluoroacetic acid (1 ml) over 2 min followed by stirring at 0° C. for 30 min. Af ter the completion of the reaction, water (0.1 ml) was added thereto and the resulting reaction solution was concentrated under reduced pressure. The resulting residue was dissolved in a 2 N aqueous solution of sodium hydroxide and stirred at room temperature for 10 min. The mixture was extracted with methylene chloride. The organic layer was separated and dried over magnesium sulfate. After concentrating the solvent under reduced pressure, the resulting residue was purified by preparative TLC to give 1-[1-(4-fluorophenethyl)piperidin-4-yl)]-6-methoxyindoline (10 mg) (yield: 35%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[C:26][Si](CC)(CC)CC)[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].CC(C)([O-])C.[K+]>CO>[CH2:12]([N:9]1[CH2:8][CH2:7][C:6]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[CH:26])([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:10]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CCOC(=O)C1(c2ccccc2C#C[Si](CC)(CC)CC)CCN(Cc2ccccc2)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1ccccc1C1(C(=O)OCC)CCN(Cc2ccccc2)CC1
Temperature: 40 °C
Yield: 57.6 %

Procedure:
To a solution of ethyl-1-benzyl-4-(2-(2-(triethylsilyl)ethynyl)phenyl)-piperidine-4-carboxylate (0.50 g, 1.1 mmol) and MeOH (10 mL), was added potassium t-butoxide (0.15 g, 1.3 mmol). The reaction mixture was heated at 40° C. for 15 hours. The reaction mixture was then concentrated in vacuo and loaded on a silica gel column and purified by Isco HPLC (0-50% EtOAc/hexane) to give the title compound as a viscous light yellow oil (0.22 g). MS m/e=348 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH:12]3[CH2:13][CH2:14][CH2:15][CH:8]2[CH2:9][C:10](=O)[CH2:11]3)=[CH:4][CH:3]=1.Cl.[NH2:20][OH:21].N1C=CC=CC=1>C(O)C>[CH3:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH:12]3[CH2:13][CH2:14][CH2:15][CH:8]2[CH2:9][C:10](=[N:20][OH:21])[CH2:11]3)=[CH:4][CH:3]=1
Reactant: NO
Reactant: Cc1ccc(CN2C3CCCC2CC(=O)C3)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: Cc1ccc(CN2C3CCCC2CC(=NO)C3)cc1
Yield: 75.4 %

Procedure:
A solution of N-(4-methylbenzyl)-9-aza-bicyclo-[3.3.1]-nonan-3-one (5 g), hydroxylamine hydrochloride (1.5 g) and pyridine (0.75 ml) in ethanol (100 ml) was heated at reflux for 1 hour. The solution was evaporated and the residue dissolved in ethyl acetate and water. It was basified with potassium carbonate and the ethyl acetate extract was separated, dried and evaporated to give the crude oxime. Recrystallisation from ethyl acetate/light petroleum gave the oxime (4 g, 77%).
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[NH:8][CH:9]=[N:10]3)[CH2:3][CH2:2]1.[C@@H:15]1(N2C=C(C)C(=O)NC2=O)[O:21][C@H:18]([CH2:19][OH:20])[CH2:17][CH2:16]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>CN(C)C=O>[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[NH:8][CH:9]=[N:10]3)[CH2:2][CH2:3]1.[CH:1]1([CH2:4][NH:5][C:6]2[N:14]=[CH:13][N:12]=[C:11]3[C:7]=2[N:8]=[CH:9][N:10]3[C@H:15]2[CH2:16][CH2:17][C@@H:18]([CH2:19][OH:20])[O:21]2)[CH2:2][CH2:3]1
Reactant: Cc1cn([C@H]2CC[C@@H](CO)O2)c(=O)[nH]c1=O
Agent: Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OC[C@@H]1CC[C@H](n2cnc3c(NCC4CC4)ncnc32)O1
Temperature: 35 °C
Yield: 154 %

Procedure:
6-(Cyclopropylmethylamino)purine was prepared by nucleophilic displacement of the chlorine group on 6-chloropurine (Sigma Chemicals. St. Louis, Mo.) by the amino group on cyclopropylmethylamine (Karl Industries, Aurora, Ohio). 6-(Cyclopropylmethylamino)purine (2.64 mmol, 0.50 g) was dissolved in 5 mL of dimethylformamide with heating. After cooling to room temperature 3'-deoxythymidine (3.98 mmol, 0.90 g) (Horwitz J. P. et al., J. Org. Chem. 31, 205 (1966)) was added along with 30 mL of 10 mM potassium phosphate buffer with a pH of 6.8 containing 0.04% potassium azide. Purified thymidine phosphorylase (10,000 I.U.) and purine nucleoside phosphorylase (20,000 I. U.) (Krenitsky T. A. et al., Biochemistry 20, 3615, 1981 and U.S. Pat. No. 4,381,4440 absorbed onto 10 mL DEAE cellulose (Whatman) were added, and the suspension was stirred at 35° C. After 8 hours the reaction was filtered, and the filtrate was applied to a series of coupled columns. The initial column contained AG1-X 2 resin (OH form), 2.5×10 cm, while the second column contained Amberlite XAD-2 resin, 2.5×20 cm. After sample application, the columns were washed with 500 mL water and the product was eluted with methanol. The product was then flash chromatographed on a silica gel column, 5×20 cm, with a mixture of chloroform:methanol (9:1, v/v). Solvent was removed in vacuo and the product gum was transferred in acetone to a vial. Lyophilization yielded 0.588 g of 6-(cyclopropylmethylamino)-9-((2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl)-9H-purine, that analysed for 0.15 water and 0.15 acetone.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].I[C:14]1[CH:19]=[CH:18][C:17](/[C:20](/[CH3:24])=[CH:21]/[CH2:22][OH:23])=[CH:16][CH:15]=1>>[OH:23][CH2:22]/[CH:21]=[C:20](/[C:17]1[CH:18]=[CH:19][C:14]([C:7]2[CH:8]=[CH:9][C:4]([C:1](=[O:3])[CH3:2])=[CH:5][CH:6]=2)=[CH:15][CH:16]=1)\[CH3:24]
Reactant: CC(=O)c1ccc(B(O)O)cc1
Reactant: C/C(=C\CO)c1ccc(I)cc1
Product: CC(=O)c1ccc(-c2ccc(/C(C)=C/CO)cc2)cc1

Procedure:
The pale yellow solid, (E)-1-[4′-(3-hydroxy-1-methyl-propenyl)-biphenyl-4-yl]-ethanone was prepared from 4-acetylphenyl boronic acid and (E)-3-(4-iodophenyl)-but-2-en-1-ol by a procedure analogous to that described in example 54a.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[O:5][CH2:6][C:7]#[N:8].[CH3:13][S:14](Cl)(=[O:16])=[O:15].C(OCC)(=O)C>N1C=CC=CC=1>[C:7]([CH2:6][O:5][C:4]1[CH:9]=[CH:10][C:11]([CH3:12])=[C:2]([NH:1][S:14]([CH3:13])(=[O:16])=[O:15])[CH:3]=1)#[N:8]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1ccc(OCC#N)cc1N
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: Cc1ccc(OCC#N)cc1NS(C)(=O)=O
Temperature: 5 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
(3-Amino-4-methylphenoxy)-acetonitrile (2.6 g) was dissolved in 10 ml of pyridine, cooled in an ice bath; 2.29 g of methanesulfonyl chloride was added; and the reaction mixture was stirred at 5° C. for 1 hour. The mixture was poured into ethyl acetate, washed with hydrochloric acid, then water, dried, and evaporated giving 3.5 g of N-(5-cyanomethoxy-2-methylphenyl)-methanesulfonamide. ##STR66##
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([CH3:16])=[C:13]([OH:15])[CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27]>CC(C)=O>[CH3:16][C:12]1[CH:11]=[CH:10][C:9]([NH:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:14][C:13]=1[O:15][CH2:24][CH:25]=[C:26]([CH3:28])[CH3:27]
Reactant: Cc1ccc(Nc2ccnc(N)n2)cc1O
Reactant: CC(C)=CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: CC(C)=CCOc1cc(Nc2ccnc(N)n2)ccc1C
Yield: 22 %

Procedure:
Following the general procedure for O-alkylation of 2-R-5-(heteroaryl-2-ylamino)phenol, 5-(2-aminopyrimidin-4-ylamino)-2-methylphenol (89 mg, 0.41 mmol) and Cs2CO3 (134 mg, 0.41 mmol) in acetone (4.1 mL) was treated with 4-bromo-2-methyl-2-butene (50 μL, 0.41 mmol) at room temperature. The title compound was obtained after purification by flash chromatography on silica gel (CH2Cl2:MeOH 6/4) in 22% yield (26 mg).