Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C)C(=O)C[NH:5][C@:6]12[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:7]1[C@@H:8]1[C@@:21]([CH3:24])([CH2:22][CH2:23]2)[C@@:20]2([CH3:25])[C@@H:11]([C@:12]3([CH3:37])[C@@H:17]([CH2:18][CH2:19]2)[C:16]([CH3:27])([CH3:26])[C:15]([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=2)=[CH:14][CH2:13]3)[CH2:10][CH2:9]1.Cl[CH2:47][CH2:48][C:49]1[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=1>>[CH3:24][C@:21]12[C@@:20]3([CH3:25])[C@@H:11]([C@:12]4([CH3:37])[C@@H:17]([CH2:18][CH2:19]3)[C:16]([CH3:26])([CH3:27])[C:15]([C:28]3[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=3)=[CH:14][CH2:13]4)[CH2:10][CH2:9][C@@H:8]1[C@H:7]1[C@H:38]([C:41]([CH3:43])=[CH2:42])[CH2:39][CH2:40][C@:6]1([NH:5][CH2:47][CH2:48][C:49]1[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=1)[CH2:23][CH2:22]2
Reactant: ClCCc1ccncc1
Reactant: C=C(C)[C@@H]1CC[C@]2(NCC(=O)N(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Product: C=C(C)[C@@H]1CC[C@]2(NCCc3ccncc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following the method described above for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)-2-oxoethylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid using 4-(2-chloroethyl)pyridine as the alkylating reagent in Step 1. The product was isolated as an off white solid (10 mg, 2.9%). LCMS: m/e 635.40 (M+H)+, 2.31 min (method 13). 1H NMR (400 MHz, METHANOL-d4) δ 8.83 (d, J=5.8 Hz, 2H), 8.06 (d, J=6.0 Hz, 2H), 7.95 (d, J=8.5 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 5.33 (d, J=4.5 Hz, 1H), 4.90 (s, 1H), 4.76 (s, 1H), 3.57-3.46 (m, 4H), 2.86-2.75 (m, 1H), 2.27-2.08 (m, 5H), 2.05-1.89 (m, 2H), 1.79 (s, 3H), 1.85-1.67 (m, 4H), 1.66-1.49 (m, 7H), 1.45-1.23 (m, 4H), 1.21 (s, 3H), 1.14 (s, 3H), 1.09 (s, 3H), 1.00 (s, 3H), 0.98 (s, 3H).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:12]#[N:13])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=O.[NH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>>[N:14]1([CH2:1][C:3]2[CH:8]=[CH:7][C:6]([C:9]3([C:12]#[N:13])[CH2:11][CH2:10]3)=[CH:5][CH:4]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: N#CC1(c2ccc(C=O)cc2)CC1
Reactant: C1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CO
Product: N#CC1(c2ccc(CN3CCCC3)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 1-(4-formylphenyl)cyclopropanecarbonitrile (0.30 g, 0.0018 mol), pyrrolidine (0.18 mL, 0.0021 mol) and sodium triacetoxyborohydride (0.74 g, 0.0035 mol) in methanol (5.0 mL, 0.12 mol) was stirred ar rt for 1 h. The reaction mixture was adjusted to be basic (pH=12) and extracted with ethyl acetate. The combined organic extract was washed with brine, dried and concentrated to provide the desired product. LC-MS: 227.1 (M+H)+
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([NH2:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:14]([N:16]1[C:20]2[CH:21]=[CH:22][C:23]([CH:25]=O)=[CH:24][C:19]=2[N:18]([CH2:27][CH3:28])[C:17]1=[O:29])[CH3:15].S([O-])([O-])(=O)=O.[Mg+2]>ClCCl>[CH2:1]([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]=[CH:25][C:23]2[CH:22]=[CH:21][C:20]3[N:16]([CH2:14][CH3:15])[C:17](=[O:29])[N:18]([CH2:27][CH3:28])[C:19]=3[CH:24]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCn1c(=O)n(CC)c2cc(C=O)ccc21
Reactant: N[C@@H]1CCN(Cc2ccccc2)C1
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Product: CCn1c(=O)n(CC)c2cc(C=N[C@@H]3CCN(Cc4ccccc4)C3)ccc21
Temperature: 22 °C
Reaction time: 20 h
Yield: 103.9 %

Procedure:
To a dry flask charged with a stir bar was added (3R)-(−)-1-benzyl-3-aminopyrrolidine (202 mg, 1.15 mmoles) (commercial from TCI-US), 1,3-Diethyl-2-oxo-2,3-dihydro-1H-benzoimidazole-5-carbaldehyde (250 mg, 1.15 mmoles), magnesium sulfate (500 mg) and 5 ml of dichloromethane (0.23 M). The flask was sealed with a plastic cap and the resulting mixture was stirred for 20 hours at 22° C. The mixture was filtered through a nylon disk via syringes, rinsing with dichloromethane and the yellow filtrate was concentrated to give 450 mg of the title compound as a yellow gum/foam.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+].Cl[C:11]([O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:12].O>CO>[C:14]1([O:13][C:11]([N:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH2:3]2)=[O:12])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Clc1cccnc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: O=C(Oc1ccccc1)N1C=CC=C(Cl)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.7 %

Procedure:
To a solution of 3-chloro-pyridine (6.0 g, 53 mmol) in methanol (50 mL) was added NaBH4 (2.6 g, 69 mmol) at −78° C., following addition of phenyl chloroformate (8.3 g, 53 mmol) at same temperature. The mixture was stirred at r.t. for 0.5 h. Then water (200 mL) was added slowly into the solution. The precipitate was collected by filtration to give crude product (Yield: 8.2 g, 67%).
Reaction SMILES: [CH2:1]1[O:15][C:4]2([CH2:9][CH2:8][C:7]([CH2:11][CH2:12][CH:13]=C)([OH:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.[BH4-].[Na+].C[OH:19]>>[CH2:1]1[O:15][C:4]2([CH2:9][CH2:8][C:7]([CH2:11][CH2:12][CH2:13][OH:19])([OH:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1
Reactant: C=CCCC1(O)CCC2(CC1)OCCO2
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Product: OCCCC1(O)CCC2(CC1)OCCO2

Procedure:
A mixture of 4-(3-butenyl)-4-hydroxy-cyclohexanone ethylene ketal (1.8 g) in methanol (40 mL) was ozonized at -70° C. until a persistent blue color was obtained. The ozonide was decomposed with excess sodium borohydride at -60° C. The reaction was concentrated in vacuo and the residue was partitioned between brine and ethyl acetate. The aqueous layer was extracted several more times with ethyl acetate and the combined organic extracts were dried over magnesium sulfate and the solvent was removed in vacuo. The residue was purified by flash chromatography with ethyl acetate as the eluent to afford 4-(3-hydroxypropyl)-4-hydroxy-cyclohexanone ethylene ketal as an oil.
Reaction SMILES: Br[C:2]1[C:3]([O:12][CH2:13][CH3:14])=[N:4][CH:5]=[N:6][C:7]=1[C:8]([F:11])([F:10])[F:9].C([Li])CCC.[CH:20](OC)=[O:21].[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH2:13]([O:12][C:3]1[C:2]([CH:20]=[O:21])=[C:7]([C:8]([F:11])([F:10])[F:9])[N:6]=[CH:5][N:4]=1)[CH3:14]
Reactant: COC=O
Reactant: CCOc1ncnc(C(F)(F)F)c1Br
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCOc1ncnc(C(F)(F)F)c1C=O
Temperature: -78 °C
Reaction time: 0.67 h
Yield: 81.5 %

Procedure:
A solution of 5.76 g (21.3 mmoles) of 5-bromo-4-ethoxy-6-trifluoromethylpyrimidine dissolved in 250 ml of THF was cooled to −78° C. Thereto was dropwise added 22.6 ml of n-butyllithium (a 1.6 moles/liter n-hexane solution, 36.1 mmoles). The mixture was stirred for 40 minutes. Thereto was added 2.7 g (45.1 mmoles) of methyl formate. The resulting mixture was stirred for 1.5 hours to give rise to a reaction. After the completion of the reaction, an aqueous ammonium chloride solution was added. The mixture was extracted with diethyl ether. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to vacuum distillation to remove the solvent contained therein. The residue was purified by silica gel column chromatography (developing solvent: hexane-ethyl acetate mixed solvent) to obtain 3.82 g (yield:. 81.6%) of 4-ethoxy-6-trifluoromethylpyrimidine-5-carboaldehyde.
Reaction SMILES: [CH3:1][C:2]([N:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:23])[CH:18]([NH2:22])[CH2:19][CH2:20][CH3:21])[N:13]=[CH:12]1)([CH3:10])[CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.[F:24][C:25]([F:37])([F:36])[C:26]1[CH:27]=[C:28]([CH2:32][C:33](O)=[O:34])[CH:29]=[CH:30][CH:31]=1>>[CH3:1][C:2]([N:11]1[CH:15]=[C:14]([NH:16][C:17](=[O:23])[CH:18]([NH:22][C:33](=[O:34])[CH2:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([C:25]([F:36])([F:24])[F:37])[CH:27]=2)[CH2:19][CH2:20][CH3:21])[N:13]=[CH:12]1)([CH3:10])[CH2:3][N:4]1[CH2:5][CH2:6][O:7][CH2:8][CH2:9]1
Reactant: O=C(O)Cc1cccc(C(F)(F)F)c1
Reactant: CCCC(N)C(=O)Nc1cn(C(C)(C)CN2CCOCC2)cn1
Product: CCCC(NC(=O)Cc1cccc(C(F)(F)F)c1)C(=O)Nc1cn(C(C)(C)CN2CCOCC2)cn1

Procedure:
2-Amino-pentanoic acid [1-(1,1-dimethyl-2-morpholin-4-yl-ethyl)-1H-imidazol-4-yl]-amide was coupled with (3-trifluoromethylphenyl)-acetic acid to afford the title compound: C13 NMR (100 MHz, CDCl3) 13.9, 18.9, 25.9, 35.9, 43.2, 53.1, 55.5, 59.2, 67.4, 68.8, 105.3, 112.5, 124.1, 124.2, 126.2, 126.3, 129.3, 131.7, 132.9, 136.1, 137.5, 169.3, 169.7; MS m/z 510.4 (M+1).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F:12][C:13]([F:24])([F:23])[C:14]1[C:22]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=2[NH:16][N:15]=1>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:16]2[C:17]3[CH2:18][CH2:19][CH2:20][CH2:21][C:22]=3[C:14]([C:13]([F:12])([F:24])[F:23])=[N:15]2)=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc(Br)cc1
Reactant: FC(F)(F)c1n[nH]c2c1CCCC2
Product: CS(=O)(=O)c1ccc(-n2nc(C(F)(F)F)c3c2CCCC3)cc1

Procedure:
The title compound was prepared from 4-bromophenyl methyl sulfone and 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole using a similar procedure to that described for Example 7.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]([CH2:22][NH2:23])[CH2:17][CH2:16][CH2:15]3)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[O:41]=[C:42](C)[CH2:43][O:44][C:45](=[O:47])[CH3:46]>C(Cl)Cl>[F:2][C:3]1[CH:4]=[C:5]([S:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][NH:23][C:42]([CH2:43][O:44][C:45](=[O:47])[CH3:46])=[O:41])[CH2:17][CH2:16][CH2:15]3)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1
Reactant: NCC1CCCc2cc(S(=O)(=O)c3cccc(F)c3)ccc21
Reactant: CC(=O)COC(C)=O
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)OCC(=O)NC[C@@H]1CCCc2cc(S(=O)(=O)c3cccc(F)c3)ccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 70.5 %

Procedure:
C-[6-(3-Fluoro-benzenesulfonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-methylamine hydrochloride (0.12 gms, 0.338 mmole), 1-hydroxybenzotriazole (0.07 g, 0.507 mmol) ethylcarbodiimide (0.10 g, 0.507 mmol), triethylamine (0.3 mL, 2.0 mmol) and acetic acid 2-oxo-propyl ester (0.05 g, 0.40 mmol) were dissolved in 10 mL methylene chloride. The reaction mixture was stirred at room temperature for 24 hours. The reaction was quenched with water, and the entire mixture was absorbed on to silica gel and medium pressure chromatography, and eluted with ethyl acetate//hexanes (3:1) to give 0.1 g of acetic acid {[(R)-6-(3-fluoro-benzenesulfonyl)-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl]-carbamoyl}-methyl ester.
Reaction SMILES: C([O:3][C:4]([CH2:6][N:7]1[C:16]2[C:11](=[CH:12][C:13]([N+:22]([O-:24])=[O:23])=[C:14]([N:17]3[CH:21]=[CH:20][CH:19]=[CH:18]3)[CH:15]=2)[NH:10][C:9](=[O:25])[C:8]1=[O:26])=[O:5])C.[OH-].[Li+]>O1CCCC1.O>[C:4]([CH2:6][N:7]1[C:16]2[C:11](=[CH:12][C:13]([N+:22]([O-:24])=[O:23])=[C:14]([N:17]3[CH:21]=[CH:20][CH:19]=[CH:18]3)[CH:15]=2)[NH:10][C:9](=[O:25])[C:8]1=[O:26])([OH:5])=[O:3]
Reactant: CCOC(=O)Cn1c(=O)c(=O)[nH]c2cc([N+](=O)[O-])c(-n3cccc3)cc21
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)Cn1c(=O)c(=O)[nH]c2cc([N+](=O)[O-])c(-n3cccc3)cc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.9 %

Procedure:
24.5 g (68 mmol) of 1-(ethoxycarbonylmethyl)-6-nitro-7-(1-pyrrolyl)-2,3(1H,4H)-quinoxalinedione (Example 52) were dissolved in 500 ml of tetrahydrofuran, and a solution of 6.6 g (270 mmol) of lithium hydroxide in 100 ml of water was added. The mixture was stirred at room temperature for 16 h and then the tetrahydrofuran was removed under reduced pressure, and the aqueous phase was filtered. The filtrate was acidified with 1M hydrochloric acid, and the precipitate was filtered off with suction to yield 17.5 g (77%) of the product.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[C:11]=2[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:22][CH:21]=2)=[CH:6][CH:5]=1.[CH2:34]([N:36](CC)CC)[CH3:35].Cl.C(=N)(OCC)C>ClCCl.CO>[NH:36]=[C:34]([NH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[S:14][C:13]3[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=3[C:11]=2[CH2:19][C:20]2[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)=[CH:24][CH:25]=2)=[CH:6][CH:5]=1)[CH3:35]
Reactant: CCN(CC)CC
Reactant: NCCc1ccc(-c2sc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
Agent: CCOC(C)=N
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CC(=N)NCCc1ccc(-c2sc3ccccc3c2Cc2ccc(OCCN3CCCC3)cc2)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
2-[4-(2-Aminoethyl)phenyl]-3-[4-[2-(1-pyrrolidinyl)ethoxy]benzyl]benzo[b]thiophene (100 mg) was dissolved in dichloromethane:methanol (2:5, 7.0 mL), treated with triethylamine (0.2 mL) and ethyl acetimidate hydrochloride (135 mg) sequentially and allowed to stir at ambient temperature for 4 h. The reaction mixture was concentrated and fractionated by column chromatography with NH4OH:MeOH:—EtOAc (10:20:70) to afford the title compound (51 mg).
Reaction SMILES: [CH3:1][C:2]1[O:16][C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[C:5]2[CH:6]=[C:7](Br)[CH:8]=[CH:9][C:4]=2[N:3]=1.Br[C:18]1[S:22][C:21]([C:23]#[N:24])=[CH:20][C:19]=1[CH3:25]>>[CH3:1][C:2]1[O:16][C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[C:5]2[CH:6]=[C:7]([C:18]3[S:22][C:21]([C:23]#[N:24])=[CH:20][C:19]=3[CH3:25])[CH:8]=[CH:9][C:4]=2[N:3]=1
Reactant: CC1=Nc2ccc(Br)cc2C2(CCCC2)O1
Reactant: Cc1cc(C#N)sc1Br
Product: CC1=Nc2ccc(-c3sc(C#N)cc3C)cc2C2(CCCC2)O1

Procedure:
The title compound was prepared according to the procedure for Example 13 from 2-methyl-6-bromospiro[4H-3,1-benzoxazine-4,1′-cyclopentane] and 5-bromo-4-methyl-2-thiophenecarbonitrile. A yellowish solid: mp 58-60° C.; 1H-NMR (DMSO-d6) δ 7.79 (s, 1H), 7.16 (d, 1H, J=1.9 Hz), 7.12 (dd, 1H, J=8.4, 2.2 Hz), 6.66 (s, 1H), 6.63 (d, 1H, J 8.4 Hz), 4.75 (m, 1H), 2.26 (s, 3H), 2.14 (m, 1H), 1.87 (m, 1H), 1.4-1.7 (m, 6H), 1.32 (d, 3H, J=5.5 Hz).
Reaction SMILES: [OH:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:11]=[C:12]([CH:14]=[CH:15][CH:16]=1)[NH2:13]>O.CC(C)=O>[Cl:9][C:10]1[CH:11]=[C:12]([NH:13][C:5]2[C:4]([NH:13][C:12]3[CH:14]=[CH:15][CH:16]=[C:10]([Cl:9])[CH:11]=3)=[N:3][C:2](=[O:1])[C:7](=[O:8])[CH:6]=2)[CH:14]=[CH:15][CH:16]=1
Reactant: Oc1cccnc1O
Reactant: Nc1cccc(Cl)c1
Solvent: CC(C)=O
Solvent: O
Product: O=C1C=C(Nc2cccc(Cl)c2)C(Nc2cccc(Cl)c2)=NC1=O
Reaction time: 2 h
Yield: 36 %

Procedure:
2,3-dihydroxypyridine (0.0027 mol), m-chloroaniline (0.0054 mol), and NaIO3 (0.0009 mol) were dissolved in 160 ml of water/acetone (80:1, v/v) solvent. The reaction mixture was stirred for 2 hours, and maintained still overnight. It was then filtered and recrystallized with chloroform. The final product was 5,6-di(m-chlorophenylamino)-2,3-pyridindione in a yellow powder. The yield was 36%-57%.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@H:12]2[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]2)=[C:5]([NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:4]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:51][C:52]1[CH:59]=[CH:58][C:55]([CH:56]=O)=[CH:54][CH:53]=1>>[Cl:51][C:52]1[CH:59]=[CH:58][C:55]([CH2:56][NH:1][CH2:2][C:3]2[N:11]=[C:10]3[C:6]([N:7]=[CH:8][N:9]3[C@H:12]3[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]3)=[C:5]([NH:22][CH2:23][CH:24]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:4]=2)=[CH:54][CH:53]=1
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@H](O)[C@@H]1O
Reactant: O=Cc1ccc(Cl)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CNCc4ccc(Cl)cc4)nc32)[C@H](O)[C@@H]1O
Yield: 21.5 %

Procedure:
The title compound was prepared by a similar method to example 5 using (2R,3R,4S,5R)-2-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino}-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (example 1) (200 mg, 0.4 mmol), sodium triacetoxyborohydride (152 mg, 0.72 mmol) and 4-chlorobenzaldehyde (75 mg, 0.53 mmol). The product was purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol (98:2) gradually increasing polarity to dichloromethane:methanol (90:10), which gave the title compound (53 mg) as a foam. MS: 615 (MH+).
Reaction SMILES: [CH3:1][C:2]1([CH3:33])[S:7][CH2:6][CH2:5][N:4]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]#[C:20][CH2:21][CH2:22][O:23][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:3]1[C:30](O)=[O:31].[OH:34][N:35]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.NO>CN(C=O)C.C(OCC)(=O)C>[OH:34][NH:35][C:30]([CH:3]1[C:2]([CH3:33])([CH3:1])[S:7][CH2:6][CH2:5][N:4]1[S:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]#[C:20][CH2:21][CH2:22][O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[CH:13][CH:12]=1)(=[O:10])=[O:9])=[O:31]
Reactant: On1nnc2ccccc21
Reactant: CC1(C)SCCN(S(=O)(=O)c2ccc(OCC#CCCOC3CCCCO3)cc2)C1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: NO
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C)SCCN(S(=O)(=O)c2ccc(OCC#CCCOC3CCCCO3)cc2)C1C(=O)NO
Temperature: 25 °C
Reaction time: 1 h
Yield: 8.4 %

Procedure:
To a solution of 0.28 g (0.56 mmol) of 2,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxylic acid and 0.091 g (0.675 mmol) of 1-hydroxybenzotriazole in 2.5 mL of DMF was added 0.151 g (0.788 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and stirred at room temperature for 1 h. Then 0.173 mL (2.8 mmol) of 50% aqueous hydroxylamine was added and the reaction was stirred for 18 h. The resulting mixture was diluted with ethyl acetate, washed with water, brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 5% methanol/dichloromethane. The product was triturated with ether to provide 0.024 g (8%) of N-hydroxy-2,2-dimethyl-4-[(4-{[5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynyl]oxy}phenyl)sulfonyl]-3-thiomorpholine carboxamide as a white solid. Electrospray Mass Spec: 513.4 (M+H)+
Reaction SMILES: Cl.[C:2](=[NH:12])([O:9][CH2:10][CH3:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl:20][CH2:21][C:22](Cl)=[O:23]>ClC(Cl)C>[Cl:20][CH2:21][C:22](/[N:12]=[C:2](\[O:9][CH2:10][CH3:11])/[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=[O:23]
Reactant: CCOC(=N)c1ccccc1
Reactant: O=C(Cl)CCl
Agent: Cl
Solvent: CC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCO/C(=N\C(=O)CCl)c1ccccc1
Temperature: 0 °C
Reaction time: 4 h
Yield: 97.4 %

Procedure:
To a suspension of ethyl benzimidate hydrochloride (500 mg, 2.69 mmol) in dichloroethane (25 mL) was added under argon atmosphere triethylamine (872 mg, 1.2 mL, 8.62 mmol). The stirred reaction mixture was cooled to 0° C. and chloroacetyl chloride (608 mg, 431 μL, 5.39 mmol) was added. After 30 min the cooling bath was removed and stirring was continued at RT for 4 h. After filtration the organic phase was extracted with KHSO4 (10% aqueous solution), dried and evaporated to yield the product as light brown semi-solid (740 mg with 80% purity, 2.62 mmol, 97%) which was used without further purification for the next step.
Reaction SMILES: [C:1]1([CH:7]([C:9]([O:11][CH:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[CH:28]=[S:29])C.S>O1CCCC1>[S:29]=[CH:28][NH:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:9]([O:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10]
Reactant: NC(C(=O)OC(c1ccccc1)c1ccccc1)c1ccccc1
Reactant: CCOC=S
Agent: S
Solvent: C1CCOC1
Product: O=C(OC(c1ccccc1)c1ccccc1)C(NC=S)c1ccccc1
Reaction time: 8 h

Procedure:
A solution of 15.9 g. (0.05 mol.) of α-phenylglycine, diphenylmethyl ester, and 9 g. of (0.1 mol.) of ethylthioformate in 50 ml. of tetrahydrofuran is stirred overnight at room temperature. Then a stream of hydrogen sulfide is passed into the solution for 10 minutes, the reaction mixture is permitted to stand overnight, then concentrated and petroleum ether is added to the residue. 16.9 g. of α-[(thioxomethyl)amino]benzeneacetic acid, diphenylmethyl ester, crystallizes. The crude product is recrystallized from methanol, m.p. 129°-130°.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(O[CH:20](N(C)C)[N:21]([CH3:23])[CH3:22])(C)(C)C>CN(C=O)C>[CH3:20][N:21]([CH3:23])/[CH:22]=[CH:1]/[C:2]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1C
Solvent: CN(C)C=O
Product: COC(=O)c1ccc([N+](=O)[O-])cc1/C=C/N(C)C
Temperature: 143 °C
Reaction time: 8 h
Yield: 70.1 %

Procedure:
To Intermediate 3A (11.35 g, 58.2 mmol) in DMF (15 ml) was added 1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (39.6 ml, 192 mmol). The mixture was heated at 143° C. for 3.0 h. DMF was removed by vacuum distillation at 70° C. to leave a semi solid. The semi-solid was triturated with EtOAc/hexanes (1:4) and stored at 4° C. overnight. The precipitate was collected by filtration to give Intermediate 3B (10.2 g, 40.8 mmol, 70.1% yield) as a dark solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.21 (d, J=2.20 Hz, 1H) 7.87 (d, J=8.79 Hz, 1H) 7.66 (dd, J=8.79, 2.20 Hz, 1H) 7.02 (d, J=13.19 Hz, 1H) 6.12 (d, J=13.74 Hz, 1H) 3.91 (s, 3H) 2.94 (s, 6H).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[CH:6]=1)=[O:4].[S-:12][C:13]#[N:14].[K+].O>C(O)C>[CH3:11][C:7]1[CH:6]=[C:5]([C:3](=[O:4])[CH2:2][S:12][C:13]#[N:14])[CH:10]=[CH:9][CH:8]=1
Reactant: Cc1cccc(C(=O)CBr)c1
Reactant: N#C[S-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: Cc1cccc(C(=O)CSC#N)c1
Temperature: 25 °C
Yield: 0.1 %

Procedure:
A solution of 2-bromo-1-(3-methylphenyl)ethanone (3.03 g, 14.2 mmol) and potassium thiocyanate (1.45 g, 14.2 mmol) in ethanol (30 ml) was stirred at 80° C. for 2 hours. After cooling to room temperature, water (30 ml) was poured to the reaction mixture, and crystals were collected by filtration and washed with water to give 2.29 mg (84.2%) of the desired product as a solid.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH:7]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])=[CH2:8].FF>C(=O)([O-])O.[Na+]>[C:1]([O:6][CH:7]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])[CH3:8])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)O
Reactant: C=COCC(C)C
Agent: FF
Agent: O=C([O-])O
Agent: [Na+]
Product: C=C(C)C(=O)OC(C)OCC(C)C
Yield: 66.1 %

Procedure:
Into a 50-mL eggplant-shaped flask, 8.61 g (100 mmol) of methacrylic acid and 20.0 g (200 mmol) of isobutyl vinyl ether were placed. A fluorine resin-coated stirring piece was dropped into the flask. The mixed solution inside the flask was heated for 6 hours by immersing the flask in an oil bath whose temperature was controlled to 60° C. while stirring the mixed solution by the stirring piece with the use of a magnetic stirrer. After the heating, the whole of the mixed solution was mixed with 20 ml of aqueous sodium hydrogencarbonate solution (concentration: 5 wt %). The resulting mixed solution was left still and separated into an organic phase and an aqueous phase. The organic phase was extracted, dried with sodium sulfate to remove therefrom moisture content, and then, filtrated. The thus-obtained filtrate was concentrated under the conditions of a temperature of 40° C. and a pressure of 30 hPa by a rotary evaporator. By this, 12.32 g of 1-(2-methylpropoxy)ethyl methacrylate of the following formula was obtained in the form of a pale yellow liquid as a protected carboxyl-containing monomer for providing a repeating unit B2 in a polymer.