Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5]2.[C:19]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=[O:46])[O:27][CH:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][N:36]([CH3:45])[C:37](=[O:44])[CH2:38][CH2:39][CH2:40][CH2:41][CH:42]=O)[CH2:30][CH2:29]1>>[C:19]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26]([O:27][CH:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][N:36]([CH3:45])[C:37](=[O:44])[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][NH:1][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5]3)[CH2:30][CH2:29]1)=[O:46]
Reactant: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCC=O
Reactant: CC(C)(C)OC(=O)N1CCc2cc(N)ccc2C1
Product: CN(CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1)C(=O)CCCCCNc1ccc2c(c1)CCN(C(=O)OC(C)(C)C)C2
Yield: 19.1 %

Procedure:
tert-Butyl 6-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate (227 mg, 0.914 mmol) and the compound (638 mg, 1.37 mmol) obtained in Example 4g were used to give the title compound (122 mg; yield, 19%) as a colorless oily substance according to the method described in Example 45b.
Reaction SMILES: [CH:1]1[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[C:17](Cl)([CH3:20])([CH3:19])[CH3:18].ClCCl.[Cl-].[Al+3].[Cl-].[Cl-]>O>[C:17]([C:9]1[CH:10]=[C:11]2[C:16]3=[C:15]4[C:4]([CH:3]=[CH:2][CH:1]=[C:14]4[CH:13]=[CH:12]2)=[CH:5][CH:6]=[C:7]3[CH:8]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: c1cc2ccc3cccc4ccc(c1)c2c34
Reactant: CC(C)(C)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)c1cc2ccc3cccc4ccc(c1)c2c34
Temperature: 25 °C
Reaction time: 3 h
Yield: 57.3 %

Procedure:
A mixed solution of 4.1 g of pyrene, 2 g of t-butyl chloride and 33 ml of dichloromethane was cooled to 0° C. under a nitrogen stream, and 2.7 g of aluminum chloride was added. After this mixed solution was stirred at room temperature for 3 hours, 30 ml of water was added, and this was extracted with 30 ml of dichloromethane. The organic layer was washed with 20 ml of water two times, dried with magnesium sulfate, and evaporated. This was purified by silica gel column chromatography, and vacuum-dried to obtain 3 g (content 65%) of 2-t-butylpyrene.
Reaction SMILES: [C:1]1([C:7]2[CH:15]=[CH:14][C:10]3[S:11][CH:12]=[CH:13][C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:17](=[O:25])[CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].Cl[Sn](Cl)(Cl)Cl>C(Cl)Cl>[O:25]=[C:17]([C:13]1[C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:15]=[CH:14][C:10]=2[S:11][CH:12]=1)[CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21]
Reactant: c1ccc(-c2ccc3sccc3c2)cc1
Reactant: CCOC(=O)CCC(=O)Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: CCOC(=O)CCC(=O)c1csc2ccc(-c3ccccc3)cc12
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 5-phenylbenzo[b]thiophene (1.05 g, 5.0 mmol, 1 eq) in DCM (100 mL) at 0° C. was added ethyl 4-chloro-4-oxobutanoate (0.9 g, 21.4 mmol). The resulting mixture was stirred at 0° C. for 30 minutes. SnCl4 (2.3 mL, 6.0 mmol, 1.2 eq) was added and the mixture was stirred at room temperature overnight. The reaction mixture was quenched with aqueous HCl solution (50 mL, 3 M) and extracted with diethyl ether. The combined organic layers were dried over Na2SO4. After filtration and concentration, the crude product was purified by column chromatography to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[NH:15][C:14]3[C:13](=[O:16])[N:12]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[C:11](=[O:25])[N:10]([CH2:26][CH2:27][CH2:28][CH3:29])[C:9]=3[N:8]=2)=[CH:4][CH:3]=1.[F:32][C:33]([F:46])([F:45])[O:34][C:35]1[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][CH:36]=1>>[CH2:26]([N:10]1[C:9]2[N:8]=[C:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][S:41]([C:38]4[CH:37]=[CH:36][C:35]([O:34][C:33]([F:32])([F:45])[F:46])=[CH:40][CH:39]=4)(=[O:43])=[O:42])=[CH:31][CH:30]=3)[NH:15][C:14]=2[C:13](=[O:16])[N:12]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C:11]1=[O:25])[CH2:27][CH2:28][CH3:29]
Reactant: O=S(=O)(Cl)c1ccc(OC(F)(F)F)cc1
Reactant: CCCCn1c(=O)n(Cc2ccccc2F)c(=O)c2[nH]c(Cc3ccc(N)cc3)nc21
Product: CCCCn1c(=O)n(Cc2ccccc2F)c(=O)c2[nH]c(Cc3ccc(NS(=O)(=O)c4ccc(OC(F)(F)F)cc4)cc3)nc21

Procedure:
Prepared from 8-(4-amino-benzyl)-3-butyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione and 4-(trifluoromethoxy)-benzenesulfonyl chloride. Purity (ELSD, based on MW=645.6)=87%.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH:12]([N:15]1[CH2:19][CH:18]([CH2:20][O:21][C:22]2[CH:23]=[N:24][C:25]([CH3:28])=[CH:26][CH:27]=2)[O:17][C:16]1=[O:29])([CH3:14])[CH3:13]>ClCCl>[CH:12]([N:15]1[CH2:19][CH:18]([CH2:20][O:21][C:22]2[CH:23]=[N+:24]([O-:9])[C:25]([CH3:28])=[CH:26][CH:27]=2)[O:17][C:16]1=[O:29])([CH3:14])[CH3:13]
Reactant: Cc1ccc(OCC2CN(C(C)C)C(=O)O2)cn1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cc1ccc(OCC2CN(C(C)C)C(=O)O2)c[n+]1[O-]
Reaction time: 8 h

Procedure:
A solution of 4.1 g of m-chloroperbenzoic acid in 30 ml of dichloromethane is added over the course of 10 minutes to a solution of 4.8 g of 3-isopropyl-5-[(6-methylpyridin-3-yloxy)methyl]-oxazolidin-2-one in 50 ml of dichloromethane, whilst stirring, and the mixture is left to stand overnight at room temperature. After dilution with 50 ml of dichloromethane the reaction mixture is extracted with 20 ml of saturated potassium bicarbonate solution at a time, dried over sodium sulphate and evaporated in vacuo. The crystalline residue is recrystallised from dichloromethane-ether. 3-[(3-Isopropyloxazolidin-2-on-5-yl)methoxy]-6-methyl-pyridine-1-oxide, thus obtained, melts at 137°-139° C.
Reaction SMILES: [CH:1]([CH:13]1[CH2:18][C:17](=[O:19])[O:16][C:14]1=[O:15])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(N(CC)CC)C.[F:27][C:28]1[CH:49]=[CH:48][CH:47]=[CH:46][C:29]=1[CH:30]=[C:31]1[C:36](=[O:37])[C:35](=[CH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])[CH2:34][NH:33][CH2:32]1>C(Cl)Cl>[F:45][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=1[CH:38]=[C:35]1[C:36](=[O:37])[C:31](=[CH:30][C:29]2[CH:46]=[CH:47][CH:48]=[CH:49][C:28]=2[F:27])[CH2:32][N:33]([C:14]([CH:13]([CH:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:18][C:17]([OH:16])=[O:19])=[O:15])[CH2:34]1
Reactant: O=C1C(=Cc2ccccc2F)CNCC1=Cc1ccccc1F
Reactant: CCCCCCCCCCC=CC1CC(=O)OC1=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCC=CC(CC(=O)O)C(=O)N1CC(=Cc2ccccc2F)C(=O)C(=Cc2ccccc2F)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Dodecenyl succinic anhydride (179 mg, 0.67 mmol) and triethylamine (0.18 ml, 1.29 mmol) were added to a solution of compound 1 (200 mg, 0.64 mmol) in dry methylene chloride and stirred at room temperature for 2 h. The mixture was chromatographed on a silica column, and the title compound 26 was eluted from the column using 10% methanol:chloroform as eluant. The compound 26 was obtained as yellow thick syrup (352 mg, 95% yield). Rf (10:90 methanol:chloroform)=0.26. 1H NMR (300 MHz, CDCl3): δ 7.90-7.80 (m, 3H, 2C═CH, vinyl-H), 7.42-7.00 (m, 9H, Ar—H, vinyl-H), 5.30-5.05 (m, 4H), 5.00-4.95 (m, 2H), 4.82-7.78 (m, 2H), 4.65-4.40 (m, 4H), 2.85-2.70 (m, 2H), 2.50-2.40 (m, 2H), 2.30-2.10 (m, 4H), 2.08-1.90 (m, 4H), 1.90-1.70 (m, 2H), 0.91 (t, 3H, J=6.4, CH3). 13C NMR (75 MHz, CDCl3): δ 185.81, 173.27, 170.15, 161.96 (d, J=55.2), 159.45 (d, J=53.7), 135.38, 134.29, 133.30, 133.10, 131.52, 130.78, 130.51, 125.33, 124.78, 124.23 (d, J=3.1), 122.47 (d, J=13.3), 122.22 (d, J=14.8), 116.32 (d, J=18.9), 116.22 (d, J=21.8), 115.93 (d, J=25.7), 46.45 (d, J=3.2), 46.48 (d, J=3.1), 35.27, 33.08, 31.92, 29.9, 29.19, 29.44, 29.16, 28.86, 25.05, 24.21, 22.67, 14.13. ESI Mass calculated for C35H41F2NNaO4 (M+Na)+600.29. found 600.20.
Reaction SMILES: [CH:1]([N:14]1[CH2:18][CH2:17][CH:16]([CH2:19][NH2:20])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]1([CH:27]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:28][C:29](O)=[O:30])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:1]([N:14]1[CH2:18][CH2:17][CH:16]([CH2:19][NH:20][C:29](=[O:30])[CH2:28][CH:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CC(c1ccccc1)c1ccccc1
Reactant: NCC1CCN(C(c2ccccc2)c2ccccc2)C1
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: ClCCl
Product: O=C(CC(c1ccccc1)c1ccccc1)NCC1CCN(C(c2ccccc2)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of C-(1-Benzhydryl-pyrrolidin-3-yl)-methylamine (0.26 g, 0.98 mmol) in dry CH2Cl2 (25 ml) was added 3,3-diphenylpropionic acid (0.22 g, 0.98 mmol) under nitrogen. To the reaction was added EDC (0.37 g, 1.95 mmol) and DMAP (cat) and the reaction mixture stirred under nitrogen at room temperature overnight. The reaction was then concentrated under reduced pressure. The residue dissolved in ethyl acetate: water (10:1) (100 ml). The organic was washed with water (20 ml, 2×) and 10% NaOH (20 ml) and dried over MgSO4 and evaporated to dryness. The resulting residue was purified by column chromatography using CH2Cl2:CH3OH (15:1) to give a desired product in good yield
Reaction SMILES: [CH3:1][C:2]1[N:3]=[N:4][N:5]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:6]=1[Si](C)(C)C.F>C1COCC1.O>[CH3:1][C:2]1[N:3]=[N:4][N:5]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=1
Reactant: CCOC(=O)Cn1nnc(C)c1[Si](C)(C)C
Agent: F
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)Cn1cc(C)nn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94.2 %

Procedure:
To a solution of 0.77 g (3.2 mmol) of ethyl [4-methyl-5-(trimethylsilyl)-1H-1,2,3-triazole-1-yl]acetate from step A above in 2 mL of THF was added 1.3 mL (32 mmol) of a solution of 50% hydrofluoric acid in water. The resulting mixture was stirred at room temperature for 3 h and then evaporated to dryness in vacuo. Next, 5 mL of a 2.0 N ammonia in methanol solution was added and then the mixture was again evaporated to dryness in vacuo. The mixture was dissolved in dichloromethane, filtered and then evaporated in vacuo to afford the title compound as a clear gum (0.51 g. 93%). 1HNMR (500 MHz, CDCl3) δ: 7.5 (s, 1H), 5.05 (s, 2H), 4.23 (m, 2H), 2.30 (s, 3H), 1.30 (m, 3H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH:11]=O)=[CH:8][C:6]=2[N:7]=1.[CH3:19][S:20]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)(=[O:22])=[O:21].COC(OC)OC.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[S:10][C:9]([CH2:11][N:26]3[CH2:27][CH2:28][N:23]([S:20]([CH3:19])(=[O:22])=[O:21])[CH2:24][CH2:25]3)=[CH:8][C:6]=2[N:7]=1
Reactant: O=Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: CS(=O)(=O)N1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: COC(OC)OC
Solvent: ClCCCl
Product: CS(=O)(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 66.3 %

Procedure:
A mixture of 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine-6-carbaldehyde (II) (1.00 g), 1-methanesulfonyl-piperazine (750 mg) and trimethylorthoformate (3.80 mL) was stirred in 1,2-dichloroethane (30 mL) for 6 hrs at room temperature. To this was added sodium triacetoxyborohydride (900 mg) and the reaction mixture was stirred for 24 hours at room temperature. The mixture was then quenched with brine, extracted with dichloromethane, dried (MgSO4) and the solvent removed in vacuo. The residue was triturated with hot ethyl acetate to yield the title compound (VI) as a white solid (1.01 g).
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[N:12]=[C:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18](NS(C4C(C)=NN(C)C=4Cl)(=O)=O)=[CH:17][CH:16]=3)[NH:10][C:9]=2[C:8](=[O:33])[N:7]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2F)[C:6]1=[O:42])[CH2:2][CH2:3][CH3:4].C(Br)C1C=CC=CC=1.NCCC1C=CC([S:60]([NH2:63])(=[O:62])=[O:61])=CC=1>>[CH2:34]([N:7]1[C:8](=[O:33])[C:9]2[NH:10][C:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([S:60]([NH2:63])(=[O:62])=[O:61])=[CH:17][CH:16]=3)=[N:12][C:13]=2[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]1=[O:42])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: CCCCn1c(=O)n(Cc2ccccc2F)c(=O)c2[nH]c(Cc3ccc(NS(=O)(=O)c4c(C)nn(C)c4Cl)cc3)nc21
Reactant: NCCc1ccc(S(N)(=O)=O)cc1
Agent: BrCc1ccccc1
Product: CCCCn1c(=O)n(Cc2ccccc2)c(=O)c2[nH]c(Cc3ccc(S(N)(=O)=O)cc3)nc21

Procedure:
Prepared by the same method as described for 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid {4-[3-butyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide (example 34) except that in step 2 benzyl bromide was used in place of 2-fluorobenzyl bromide and in step 3 4-(2-amino-ethyl)-benzenesulfonamide was used in place of 2-(4-nitro-phenyl)-ethylamine hydrochloride salt. 4-(1-Benzyl-3-butyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl)-benzenesulfonamide was obtained as a colorless solid; LRMS for C23H25N5O4S (M+H)+ at m/z=468.27.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10](=O)[C:11]([F:14])([F:13])[F:12])=[CH:4][CH:3]=1.[NH2:17][C:18]1[C:22]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[CH:24]=2)=[CH:21][NH:20][N:19]=1>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[N:19]3[N:20]=[CH:21][C:22]([C:23]4[CH:28]=[CH:27][N:26]=[C:25]([CH3:29])[CH:24]=4)=[C:18]3[N:17]=2)=[CH:4][CH:3]=1
Reactant: Cc1cc(-c2c[nH]nc2N)ccn1
Reactant: O=C(CC(=O)C(F)(F)F)c1ccc(Br)cc1
Product: Cc1cc(-c2cnn3c(C(F)(F)F)cc(-c4ccc(Br)cc4)nc23)ccn1
Yield: 43.4 %

Procedure:
Reaction of 1-(4-bromo-phenyl)-4,4,4-trifluoro-butane-1,3-dione (148 mg, 0.5 mmol), prepared from commercially available 4-bromo-acetophenone according to general procedure A, and 3-amino-4-(2-methyl-4-pyridinyl)-pyrazole [prepared from 4-cyanomethyl-2-methyl-pyridine, as described in Bioorg. Med. Chem. Lett. 12 (2002) 3537-3541] (87 mg, 0.5 mmol) according to general procedure B yielded the title compound as a yellow solid (94 mg, 43%). MS (ISP) 433.3 [(M+H)+]; mp 226° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](Cl)=[N:7][N:6]=[CH:5]2.[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[N:7][N:6]=[CH:5]2
Reactant: Clc1nncc2cc(Br)ccc12
Reactant: C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Brc1ccc2c(N3CCCCC3)nncc2c1
Temperature: 180 °C
Reaction time: 0.33 h
Yield: 108.5 %

Procedure:
A mixture of 6-bromo-1-chlorophthalazine (Example 1, 0.1 g, 0.41 mmol), piperidine (0.081 mL, 0.82 mmol) and potassium carbonate (0.056 g, 0.41 mmol) in 5 mL acetonitrile was added to a glass microwave reaction vessel. The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 180° C. for 20 min. After about 20 min., all starting material was converted to product (M+1=292, 294). The mixture was concentrated under vacuum and purified via flash chromatography (silica gel) eluting with a gradient of 2% 2 M ammonia in MeOH/DCM to 6% 2 M ammonia in MeOH/DCM to give (0.13 g) 6-bromo-1-(piperidin-1-yl)phthalazine as yellow solid. Found MS (ES+): 292, 294(M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:14])[CH2:4][CH:5]1[CH:9]2[NH:10][C:11](=[O:13])[CH2:12][CH:8]2[CH2:7][CH2:6]1.[OH-].[Na+]>>[O:13]=[C:11]1[NH:10][CH:9]2[CH:5]([CH2:4][C:3]([OH:14])=[O:2])[CH2:6][CH2:7][CH:8]2[CH2:12]1
Reactant: COC(=O)CC1CCC2CC(=O)NC21
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)CC1CCC2CC(=O)NC12
Temperature: 50 °C
Reaction time: 0.25 h

Procedure:
Hexahydro-2-oxocyclopenta[b]pyrrole-6-acetic acid methyl ester (3aα, 6β, 6aα), 2.2 g (0.011 m), is treated with 11 ml of 1N sodium hydroxide solution with stirring at 50° C. for 15 minutes. The reaction mixture is extracted with diethyl ether and the agueous layer is passed through a Dowex-acid column. Concentration of the eluate followed by filtration of the crystals yields hexahydro-2-oxocyclopenta[b]-pyrrole-6-acetic acid (3aα, 6β, 6aα) with a melting point of 186°-189° C.
Reaction SMILES: [C:1]1([S:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCOCC1.[NH2:17][N:18]1[CH2:22][CH2:21][NH:20][C:19]1=[O:23].[OH-].[Na+]>O>[O:23]=[C:19]1[NH:20][CH2:21][CH2:22][N:18]1[NH:17][C:8](=[O:9])[S:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NN1CCNC1=O
Reactant: O=C(Cl)Sc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(NN1CCNC1=O)Sc1ccccc1

Procedure:
3.2 ml. of (phenylthio)carbonyl chloride are dissolved in 30 ml. of dioxane and a solution of 2.63 g. of 1-amino-2-imidazolidinone in a mixture of 10 ml. of dioxane and 10 ml. of water is added. 2N sodium hydroxide solution is added dropwise at room temperature so that the pH is about 7.5-8.0. About 15 ml. of 2N sodium hydroxide are required. The dioxane is then distilled off. An oil separates which crystallizes after a short while to give 3.2 g. of (2-oxo-1-imidazolidinyl)carbamothioic acid, S-phenyl ester, m.p. 154°-159° (after recrystallization from ethyl acetate).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH2:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:7][C:5]=1[NH2:6])([O-])=O.[C:20]([NH:24][C:25]#N)([O:22][CH3:23])=[O:21]>>[CH:14]1([CH2:13][CH2:12][S:11][C:8]2[CH:9]=[CH:10][C:4]3[N:1]=[C:25]([NH:24][C:20]([O:22][CH3:23])=[O:21])[NH:6][C:5]=3[CH:7]=2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: Nc1cc(SCCC2CCCCC2)ccc1[N+](=O)[O-]
Reactant: COC(=O)NC#N
Product: COC(=O)Nc1nc2ccc(SCCC3CCCCC3)cc2[nH]1

Procedure:
Repeating the reaction of Example 1 but using 10.0 g. of cyclohexylethylthiol gives 2-nitro-5-cyclohexylethylthioaniline. The nitro compound is reduced. The reduction mixture is reacted with carbomethoxycyanamide as described to give 5-cyclohexylethylthio-2-carbomethoxyaminobenzimidazole.
Reaction SMILES: [C:1]1([CH2:7][CH:8]([NH:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9]Cl)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.NC(N)=[S:22].[OH-].[Na+].Cl>C(O)C.O>[C:1]1([CH2:7][CH:8]([NH:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9][SH:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(NC(CCl)Cc1ccccc1)c1ccccc1
Reactant: NC(N)=S
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(NC(CS)Cc1ccccc1)c1ccccc1

Procedure:
80.4 millimole (mm) of 3-phenyl-2-benzamido-1-chloropropane and 80.4 mm of thiourea are dissolved in 300 ml of ethanol. The resulting solution is refluxed for three hours. 6.7 g of sodium hydroxide is dissolved in 40 ml of water and is added under an inert atmosphere to the solution which is thereafter refluxed for an additional 21/2 hours. The solution is then cooled and acidified to pH 1 with 1 N HCl. The resulting mixture is then poured over ice to yield a precipitate which is collected by filtration and then dissolved in chloroform. The chloroform is dried with magnesium sulfate and then evaporated to yield the solid 3-phenyl-2-benzamido-1-propanethiol.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[CH2:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1)=[O:9].[C:16]1([CH3:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Br)C1C=CC=CC=1>[CH2:22]([N:13]1[CH2:12][CH:11]=[C:10]([CH:8]([OH:9])[CH2:7][C:3]2[S:4][CH:5]=[CH:6][C:2]=2[CH3:1])[CH2:15][CH2:14]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Cc1ccsc1CC(=O)c1ccncc1
Reactant: Cc1ccccc1
Agent: BrCc1ccccc1
Product: Cc1ccsc1CC(O)C1=CCN(Cc2ccccc2)CC1
Temperature: 110 °C
Reaction time: 7 h
Yield: 73 %

Procedure:
After dissolving 2.72 g of 2-(3-methyl-2-thienyl)-1-(4-pyridyl)ethanone in 15 ml of toluene, 1.79 ml of benzyl bromide was added, the mixture was stirred for 7 hours at 110° C. and the precipitate was filtered out. The filtered substance was dissolved in 60 ml of methanol, 1.42 g of sodium borohydride was added in small portions at a time while cooling on ice, and the mixture was stirred for 1 hour. The reaction solution was distilled off under reduced pressure, water was added, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (2.85 g, 73% yield).
Reaction SMILES: [CH3:1][O:2][C@@H:3]1[C@H:8]([O:9][CH3:10])[C@@H:7]([O:11][CH3:12])[C@H:6]([CH3:13])[O:5][C@H:4]1[O:14][NH2:15].CCN(C(C)C)C(C)C.Cl[CH:26]([C:31]([O-])=[O:32])[C:27]([O:29][CH3:30])=[O:28]>ClCCl>[CH3:30][O:29][C:27](=[O:28])[CH2:26][C:31]([NH:15][O:14][C@H:4]1[C@H:3]([O:2][CH3:1])[C@H:8]([O:9][CH3:10])[C@@H:7]([O:11][CH3:12])[C@H:6]([CH3:13])[O:5]1)=[O:32]
Reactant: COC(=O)C(Cl)C(=O)[O-]
Reactant: CO[C@@H]1[C@@H](OC)[C@H](C)O[C@@H](ON)[C@@H]1OC
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)CC(=O)NO[C@@H]1O[C@@H](C)[C@H](OC)[C@@H](OC)[C@H]1OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 57.9 %

Procedure:
To a solution of O-((2S,3R,4R,5S,6S)-3,4,5-trimethoxy-6-methyl-tetrahydropyran-2-yl)-hydroxylamine (P-4; 157 mg, 0.71 mmol) in dichloromethane (CH2Cl2; 8 mL) was added DIEA (230 μL, 1.3 mmol) followed by a solution of methyl chloromalonate (137 mg, 1.0 mmol) dissolved in CH2Cl2 (2 mL). This mixture was allowed to stir at room temperature for 4 h. The mixture was then diluted with CH2Cl2 and washed with 1 N HCl. The aqueous fraction was extracted with CH2Cl2. The organic fractions were combined, dried with anhydrous Na2SO4 and evaporated at room temperature under vacuum. The resulting crude material was purified by silica gel chromatography (eluting with 75% EtOAc in Hexane). The title product (132 mg, 58%) was isolated as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 10.00-9.38 (m, 1H), 5.06 (d, J=55.9 Hz, 1H), 4.02-2.92 (m, 18H), 1.39 (t, J=20.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 189.13, 101.59, 81.56, 77.24, 75.39, 69.66, 59.26, 57.89, 52.86, 39.75, 26.47, 17.85; ESIMS m/z 320 (M−H).
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([C:9]2[N:14]3[N:15]=[CH:16][C:17]([C:18]([NH2:20])=[O:19])=[C:13]3[NH:12][CH2:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.C(=O)=O.CC(C)=O.[H-].[Na+].[C:32](N1C=CN=C1)(N1C=CN=C1)=[S:33]>O1CCCC1>[S:33]=[C:32]1[N:12]2[C:13]3[N:14]([C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:21])([F:1])[F:22])[CH:4]=4)=[CH:10][CH2:11]2)[N:15]=[CH:16][C:17]=3[C:18](=[O:19])[NH:20]1
Reactant: NC(=O)c1cnn2c1NCC=C2c1cccc(C(F)(F)F)c1
Reactant: S=C(n1ccnc1)n1ccnc1
Agent: O=C=O
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: O=c1[nH]c(=S)n2c3c1cnn3C(c1cccc(C(F)(F)F)c1)=CC2
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 82.2 %

Procedure:
To a stirred solution of 1.00 g of 4,5-dihydro-7-[3-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (prepared as described in Example 4) in 30 ml of dry tetrahydrofuran cooled to -78° C. (dry ice-acetone) was added 286 mg of 60% sodium hydride (dispersion in mineral oil). The reaction mixture was stirred at -78° C. for 30 minutes then 637 mg of 1,1'-thiocarbonyldiimidazole was added. The mixture was allowed to slowly warm to room temperature and was stirred for 36 hours. The reaction mixture was quenched with water, neutralized with 5% aqueous hydrochloric acid and extracted with chloroform. Evaporation of the solvent in vacuo gave 934 mg of the desired product as a yellow solid, m.p. 251°-258° C. (dec).