Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11]([C:15]1[CH:31]=[CH:30][C:18]([CH2:19][N:20]2[C:28]3[C:23](=[CH:24][C:25]([NH2:29])=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C.CCCCCC>C(Cl)Cl.CCOC(C)=O>[C:11]([C:15]1[CH:31]=[CH:30][C:18]([CH2:19][N:20]2[C:28]3[C:23](=[CH:24][C:25]([NH:29][S:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)(=[O:9])=[O:8])=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)=[CH:17][CH:16]=1)([CH3:14])([CH3:12])[CH3:13]
Reactant: CC(C)(C)c1ccc(Cn2ccc3cc(N)ccc32)cc1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCCC
Solvent: ClCCl
Product: CC(C)(C)c1ccc(Cn2ccc3cc(NS(=O)(=O)c4ccccc4)ccc32)cc1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 93.4 %

Procedure:
Benzenesulfonyl chloride (0.56 g, 3.12 mmol) was added in one portion to 1-(4-tert-butylbenzyl)-5-amino-1H-indole (0.84 g, 3.02 mmol) and diisopropylethylamine (0.43 g, 3.17 mmol) in CH2Cl2 (20 ml) at 0° C. under a nitrogen atmosphere. The resulting yellow solution was stirred at 0° C. for 5 minutes and then at room temperature for 2 hours. The reaction was quenched with water (2 ml) and then concentrated in vacuo to a brown powder. The powder was partitioned between EtOAc (15 ml) and std NaHCO3 (10 ml). All organics were combined, extracted with water (10 ml) and brine (10 ml), dried with MgSO4, filtered and concentrated in vacuo to a brown powder. Gradient SiO2 chromatography (Hexane:EtOAc) afforded N-[1-(4-tert-butyl-benzyl)-1H-indol-5-yl]-benzenesulfonamide as a brown powder (1.18 g, 94% yield): MS (ESI) m/z 419, MS (ESI) m/z 417.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:19]2[NH:20][C:21]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)([C:24]([NH:26][CH3:27])=[O:25])[CH2:22][O:23][C:18]=2[CH:17]=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C>O1CCCC1>[CH3:27][NH:26][C:24]([C:21]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)[N:20]2[C:2](=[O:4])[NH:13][C:14]3=[CH:15][CH:16]=[CH:17][C:18](=[C:19]23)[O:23][CH2:22]1)=[O:25]
Reactant: CNC(=O)C1(c2ccccn2)COc2cccc(N)c2N1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CNC(=O)C1(c2ccccn2)COc2cccc3[nH]c(=O)n1c23
Reaction time: 1 h
Yield: 249.8 %

Procedure:
Triphosgene (10 mg, 0.04 mmol) was added to a solution of 5-amino-N-methyl-3-pyridin-2-yl-3,4-dihydro-2H-1,4-benzoxazine-3-carboxamide (30 mg, 0.1 mmol) in tetrahydrofuran (3 mL) and N,N-diisopropylethylamine (40 μL, 0.2 mmol) at room temperature and was stirred for 1 h. The reaction mixture was then partitioned between ethyl acetate and water, and the organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give crude N-methyl-2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazine-4-carboxamide as a semisolid (0.031 g, 100%). LCMS calculated for C16H15N4O3 (M+H)+: m/z=311.1. found: 311.1.
Reaction SMILES: Cl.[O:2]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH2:18])[CH2:8][CH2:7]2)[O:5][CH2:4][CH2:3]1.[C:19]([NH:22][C:23]1[CH:32]=[CH:31][C:26]([S:27](Cl)(=[O:29])=[O:28])=[CH:25][CH:24]=1)(=[O:21])[CH3:20]>>[O:5]1[C:6]2([CH2:11][CH2:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:18][S:27]([C:26]3[CH:25]=[CH:24][C:23]([NH:22][C:19](=[O:21])[CH3:20])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[CH2:8][CH2:7]2)[O:2][CH2:3][CH2:4]1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccccc1N1CCC2(CC1)OCCO2
Agent: Cl
Product: CC(=O)Nc1ccc(S(=O)(=O)Nc2ccccc2N2CCC3(CC2)OCCO3)cc1

Procedure:
The title compound was prepared from 2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-phenylamine hydrochloride (which was obtained in Example 220) and N-acetylsulfanilyl chloride according to the procedure of Example 215 as a crystalline solid; 1H NMR (300 MHz, DMSO-d6) δ 1.73 (t, J=5.4 Hz, 4H), 2.73 (t, J=5.4 Hz, 4H), 3.33 (s, 4H), 3.89 (s, 3H), 7.00-7.10 (m, 2H), 7.10-7.20 (m, 1H), 7.30-7.40 (m, 1H), 7.67 (d, J=9.3 Hz, 2H), 7.71 (d, J=9.3 Hz, 2H), 8.79 (s, 1H), 10.29 (s, 1H); MS (ES) m/z: 432.2 (MH+); HRMS Calcd. for C21H26N3O5S (MH+): 432.1593. Found: 432.1597. Anal. Calcd. for C21N25N3O5S: C, 58.45; H, 5.84; N, 9.74. Found: C, 58.41; H, 5.83; N, 9.72.
Reaction SMILES: [N:1]1([C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:31])[C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]3[CH:21]=[C:22]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=4)[N:23]=[C:17]3[N:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1.[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[N:1]1([C:5]([C:7]2[CH:8]=[N:9][N:10]([CH3:31])[C:11]=2[C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]3[CH:21]=[C:22]([C:24]4[CH:25]=[C:26]([C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)[CH:27]=[CH:28][CH:29]=4)[N:23]=[C:17]3[N:16]=2)=[O:13])=[O:6])[CH2:4][CH2:3][CH2:2]1
Reactant: OB(O)c1ccccc1
Reactant: Cn1ncc(C(=O)N2CCC2)c1C(=O)Nc1ccn2cc(-c3cccc(Br)c3)nc2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ncc(C(=O)N2CCC2)c1C(=O)Nc1ccn2cc(-c3cccc(-c4ccccc4)c3)nc2n1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
Under an atmosphere of argon, in a 25 mL round-bottomed flask, 4-(azetidine-1-carbonyl)-N-(2-(3-bromophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide (85 mg, 177 μmol, Eq: 1.00, example 117), phenylboronic acid (43.2 mg, 354 μmol, Eq: 2), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (14.5 mg, 17.7 μmol, Eq: 0.1) and potassium carbonate (73.4 mg, 531 μmol, Eq: 3) were combined with DMF (2 ml) and water (0.2 ml) to give a brown solution. The reaction was stirred for 1 h at 100° C. The HPLC-MS showed complete conversion. The reaction mixture was poured into 20 mL water and extracted with EtOAc (2×25 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo. After the addition of 2 ml Methanol the desired product crystallized. The suspension was filtered off and washed with 0.5 ml MeOH. The residual solvent was removed under vacuum. The title compound was obtained as a light brown solid (42 mg, 49.7%). 4-(Azetidine-1-carbonyl)-N-(2-(3-bromophenyl)imidazo[1,2-a]pyrimidin-7-yl)-1-methyl-1H-pyrazole-5-carboxamide was prepared in analogy to example 29, using 2-(3-bromo-phenyl)-imidazo[1,2-a]pyrimidin-7-ylamine in the first step. 2-(3-Bromo-phenyl)-imidazo[1,2-a]pyrimidin-7-ylamine can be prepared in analogy to example 1, step 1, from 2-bromo-1-(3-bromo-phenyl)-ethanone.
Reaction SMILES: [OH:1][C:2]1[C:3]([O:24]C)=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[CH:7]([CH2:8][C:9]4[C:18]([Cl:19])=[CH:17][C:16]([O:20]C)=[C:15]([OH:22])[C:10]=4[CH2:11]3)[C:6]=2[CH:23]=1.B(Br)(Br)Br.O>C(Cl)Cl>[OH:1][C:2]1[C:3]([OH:24])=[CH:4][C:5]2[CH2:14][CH2:13][N:12]3[CH:7]([CH2:8][C:9]4[C:18]([Cl:19])=[CH:17][C:16]([OH:20])=[C:15]([OH:22])[C:10]=4[CH2:11]3)[C:6]=2[CH:23]=1
Reactant: COc1cc2c(cc1O)C1Cc3c(Cl)cc(OC)c(O)c3CN1CC2
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: Oc1cc2c(cc1O)C1Cc3c(Cl)cc(O)c(O)c3CN1CC2
Reaction time: 1 h
Yield: 68.1 %

Procedure:
A product obtained in Example 1 (0.3 g, 0.66 mmol) was dissolved in CH2Cl2 (20 ml), adding a solution of BBr3 (0.32 ml) in CH2Cl2 (5 ml) under ice-salt bath. The mixture was stirred for 1 hours at this temperature, then stirred at room temperature overnight. The reactant solution produced yellow precipitate. The mixture was poured into water and stirred for 30 minute. After filtering, the solid was dissolved with methanol. Then the mixture was filtered. The filtrate was evaporated under reduced pressure, followed by recrystallizing with methanol to give yellow solid (0.15 g, 67.7%). mp 295˜296° C. 1HNMR (DMSO-d6) δ: 2.65˜2.86 (3H, m, CH2), 3.05˜3.63 (5H, m, CH2 or N—CH), 4.29 (1H, d, CH2), 6.59 (1H, s, ArH), 6.81 (1H, s, ArH), 6.92 (1H, s, ArH). MS (EI) m/z: 333 (M+), 299, 164 (base), 107, 80.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18](Br)[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CO.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([OH:32])=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)COc1ccc(Cl)cc1C1c2sc(Br)nc2CCN1C(=O)OCc1ccccc1
Reactant: OB(O)c1ccccc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CO
Product: O=C(O)COc1ccc(Cl)cc1C1c2sc(-c3ccccc3)nc2CCN1C(=O)OCc1ccccc1
Temperature: 100 °C
Reaction time: 18 h

Procedure:
To a mixture under N2 of (±)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester (63 mg, 0.12 mmol, 1.00 eq.), phenylboronic acid (15 mg, 0.12 mmol, 1.00 eq.) and sodium carbonate (50 mg, 0.47 mmol, 4.00 eq.) in toluene/MeOH/Water 20:4:1 (4 mL), tetrakis(triphenylphosphine) palladium (0) (6.8 mg, 6 μmol, 0.05 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (25 mL) and water (25 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×12 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue was dissolved in DMF (0.5 mL), 1M aq. NaOH soln. (0.5 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL), filtered, and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired acid as a white solid.
Reaction SMILES: [C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[C:3]([S:7](Cl)(=[O:9])=[O:8])[CH:2]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:23]=[C:24]([O:28][CH3:29])[C:25]=1[O:26][CH3:27])[NH2:22].C(N(CC)CC)C.O>CN(C=O)C>[CH3:29][O:28][C:24]1[CH:23]=[C:21]([NH:22][S:7]([C:3]2[CH:2]=[C:1]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:6]=[CH:5][CH:4]=2)(=[O:9])=[O:8])[CH:20]=[C:19]([O:18][CH3:17])[C:25]=1[O:26][CH3:27]
Reactant: O=S(=O)(Cl)c1cccc(-c2ccccc2)c1
Reactant: COc1cc(N)cc(OC)c1OC
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(NS(=O)(=O)c2cccc(-c3ccccc3)c2)cc(OC)c1OC
Reaction time: 8 h
Yield: 91.8 %

Procedure:
A mixture of 65 mg of biphenyl-3-sulfonyl chloride (0.25 mmol), 44 mg of 3,4,5-trimethoxyaniline (0.24 mmol), and 0.3 mmol of triethylamine in 5 mL DMF was stirred overnight. The reaction mixture was treated with water and extracted with ethyl acetate. After a conventional workup, column chromatography (silica gel, petroleum ether/ethyl acetate) gave 88 mg compounds (4d) (91.7%). 1H NMR (500 MHz, CDCl3) δ 7.96 (t, 1H, J=1.8 Hz), 7.81-7.74 (m, 2H), 7.57-7.40 (m, 6H), 6.33 (s, 2H), 3.86 (s, 3H), 3.80 (s, 6H). MS (ESI) m/z 422.1 (M+Na)+.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([CH2:13][C:14](O)=[S:15])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[NH2:19][CH2:20][CH2:21][OH:22]>>[OH:22][CH2:21][CH2:20][NH:19][C:14](=[S:15])[CH2:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][C:5]2[CH:17]=[CH:18][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:8][CH:9]=1
Reactant: OC(=S)Cc1ccc(Oc2ccc(Cl)cc2)cc1
Reactant: NCCO
Product: OCCNC(=S)Cc1ccc(Oc2ccc(Cl)cc2)cc1

Procedure:
On subjecting the acid of Example 10 to an amidification reaction with 2-amino-ethanol in accordance with the working method described in Example 7, CRL 40,272 is obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([NH:13][C:14](=[O:16])[CH3:15])=[N:10][CH:9]=2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[NH:35][C:34]([C@@H:36]4[CH2:40][CH2:39][CH2:38][N:37]4[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[N:33][CH:32]=3)=[CH:27][CH:26]=2)O1.C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([NH:13][C:11]1[NH:12][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:25]3[CH:26]=[CH:27][C:28]([C:31]4[NH:35][C:34]([C@@H:36]5[CH2:40][CH2:39][CH2:38][N:37]5[C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[N:33][CH:32]=4)=[CH:29][CH:30]=3)=[CH:3][CH:4]=2)=[CH:9][N:10]=1)(=[O:16])[CH3:15]
Reactant: CC(=O)Nc1ncc(-c2ccc(Br)cc2)[nH]1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1c1ncc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)[nH]1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC(=O)Nc1ncc(-c2ccc(-c3ccc(-c4cnc([C@@H]5CCCN5C(=O)OC(C)(C)C)[nH]4)cc3)cc2)[nH]1
Temperature: 125 °C

Procedure:
A mixture of N-(5-(4-bromophenyl)-1H-imidazol-2-yl)acetamide (0.604 g, 2.16 mmol), (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (0.950 g, 2.16 mmol), NaHCO3 (0.636 g, 7.57 mmol) in DME (20 mL) and H2O (5 mL) was degassed by evacuating and back-filling with N2 (×3). To this solution Pd(PPh3)4 (0.125 g, 0.11 mmol) was added and the suspension heated at 125° C. for 24 h. The mixture was evaporated to dryness in vacuo and the residue was purified by column chromatography (Biotage) eluting with a gradient of 0 to 10% MeOH in CH2C2. The material was then purified by prep HPLC (CH3CN—H2O—NH4OAc) to afford the title compound as a colorless solid. 7.76 (app dd, J=8.4, 2.2 Hz, 4H), 7.69 (app d, J=8.4 Hz, 2H), 7.66 (app d, J=8.4 Hz, 2H), 7.45 (s, 1H), 7.23 (s, 1H), 3.66-3.72 (m, 1H), 3.48-3.53 (s, 1H), 2.34-2.46 (m, 1H), 2.18 (s, 3H), 1.96-2.10 (m, 3H), 1.46, 1.25 (s, 9H, rotamers, 1:2 ratio). LCMS: Anal. Calcd. for C29H32N6O3: 512; found: 513, 282 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Br.[C:10]1([CH:16]2[O:21][CH2:20][CH2:19][NH:18][CH2:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:18]1[CH2:19][CH2:20][O:21][CH:16]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:17]1
Reactant: c1ccc(C2CNCCO2)cc1
Reactant: BrCc1ccccc1Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Brc1ccccc1CN1CCOC(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.7 %

Procedure:
1.877 g of 2-Bromobenzyl bromide and 1 g of 2-Phenyl-morpholine in 15 mL of acetonitrile were stirred at room temperature and 2.076 g of potassium carbonate was added. The reaction was stirred at room temperature overnight. The solution was filtered through Celite and concentrated in vacuo to afford a brown solid. Purification by flash chromatography afforded 1.052 g of product. 63% yield ES MS m/z 332
Reaction SMILES: [S:1]([CH2:9][CH2:10][C:11](O)=O)([CH2:4][CH2:5][C:6](O)=O)(=[O:3])=[O:2].[NH2:14][NH:15][C:16]([NH2:18])=[S:17].[OH-].[K+]>>[S:1]([CH2:9][CH2:10][C:11]1[S:17][C:16]([NH2:18])=[N:15][N:14]=1)([CH2:4][CH2:5][C:6]1[S:17][C:16]([NH2:18])=[N:15][N:14]=1)(=[O:3])=[O:2]
Reactant: O=C(O)CCS(=O)(=O)CCC(=O)O
Reactant: NNC(N)=S
Agent: [K+]
Agent: [OH-]
Product: Nc1nnc(CCS(=O)(=O)CCc2nnc(N)s2)s1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 20 %

Procedure:
3,3′-sulfonyldipropanoic acid (1 equivalent) and thiosemicarbazide (2 equivalents) were taken in PPA and refluxed for overnight. The reaction mixture was then cooled to room temperature. The pH of the reaction mixture was adjusted to 14 using aq. KOH solution, stirred for 30 min and filtered off the solid. The Solid obtained was triturated with diethyl ether and dried to afford the title compound I-15 in 20-30% yield.
Reaction SMILES: Cl.[CH2:2]([N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=[C:10]1[CH2:18]Cl)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N-:20]=[N+:21]=[N-:22].[Na+]>CN(C)C=O.O>[CH2:2]([N:9]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=[C:10]1[CH2:18][N:20]=[N+:21]=[N-:22])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: [N-]=[N+]=[N-]
Reactant: ClCc1nc2ccccc2n1Cc1ccccc1
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: [N-]=[N+]=NCc1nc2ccccc2n1Cc1ccccc1
Yield: 72.5 %

Procedure:
A solution of 1-Benzyl-2-chloromethylbenzimidazole hydrochloride (16 g, 0.055 mole) in N,N-dimethylformamide (80 ml) was stirred and a solution of sodium azide (17 g, 0.26 mole) in water (40 ml) was added. The resulting yellow solution was heated on a steam bath for 30 minutes, diluted with water (250 ml) and the crystalline product was filtered, dried in vacuo at room temperature, and recrystallized from 2-propanol to yield 10.5 g (73%) of product: mp 108°-110°.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=4)[N:27]=3)[CH2:18]2)[N:3]=1.[NH2:36][NH2:37]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:36][NH:37]3)=[CH:14][CH:15]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH:19]([C:23]3[NH:24][CH:25]=[C:26]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[CH:29]=4)[N:27]=3)[CH2:18]2)[N:3]=1
Reactant: NN
Reactant: COc1cccc(-c2c[nH]c(C3CN(c4cc(-c5ccc(C#N)c(F)c5)nc(N)n4)CCO3)n2)c1
Solvent: CCO
Product: COc1cccc(-c2c[nH]c(C3CN(c4cc(-c5ccc6c(N)n[nH]c6c5)nc(N)n4)CCO3)n2)c1
Reaction time: 1 h
Yield: 3.5 %

Procedure:
A mixture of 4-[2-amino-6-(2-{4-[3-(methyloxy)phenyl]-1H-imidazol-2-yl}-4-morpholinyl)-4-pyrimidinyl]-2-fluorobenzonitrile (700 mg, 1.485 mmol) and hydrazine (2.35 mL, 74.2 mmol) in ethanol (8.0 mL) was heated under microwave conditions with stirring for 1 hour. The mixture was concentrated, and water (20 mL) was added. The resulting mixture was filtered to afford the crude title compound (725 mg) as a yellow solid. This material was combined with another sample of the title compound (25 mg). The combined material was washed with CH2Cl2 (2×25 mL) and EtOAc (2×20 mL), and dried under high vacuum to afford the title compound (216 mg) as a yellow solid. LC-MS (ES) m/z=484 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.08-3.15 (m, 1H), 3.23 (d, J=8.8 Hz, 1H), 3.69-3.76 (m, 1H), 3.79 (s, 3H), 4.05 (d, J=11.2 Hz, 1H), 4.33 (d, J=9.6 Hz, 1H), 4.62 (dd, J=10.0 Hz, 2.4 Hz, 1H), 4.73 (s, 1H), 5.38 (s, 2H), 6.21 (s, 2H), 6.71 (s, 1H), 6.76 (d, J=8.2 Hz, 1H), 7.25 (t, J=8.0 Hz, 1H), 7.35-7.37 (m, 2H), 7.54-7.63 (m, 2H), 7.71 (d, J=8.4 Hz, 1H), 7.97 (s, 1H), 11.52 (s, 1H), 12.34 (s, 1H).
Reaction SMILES: [CH:1]([CH:3]([O:6][CH:7]([N:10]1[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]1=[O:17])[CH:8]=[O:9])[CH2:4][OH:5])=[O:2].[NH2:18][C:19]1[S:20][CH:21]=[N:22][N:23]=1>CO.O>[OH:9][CH:8]1[C@H:7]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]2=[O:17])[O:6][C@H:3]([CH2:4][OH:5])[CH:1]([OH:2])[N:18]1[C:19]1[S:20][CH:21]=[N:22][N:23]=1
Reactant: O=CC(CO)OC(C=O)n1ccc(=O)[nH]c1=O
Reactant: Nc1nncs1
Solvent: O
Solvent: CO
Product: O=c1ccn([C@@H]2O[C@H](CO)C(O)N(c3nncs3)C2O)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 4 h
Yield: 88.4 %

Procedure:
[R-(R*, R*)]-α-(1-Formyl-2-hydroxyethoxy)-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidineacetaldehyde, (uridinedialdehyde), (2.42 g) was dissolved in a mixture of methanol (50 ml) and water (50 ml). To the solution was added 2-amino-1,3,4-thiadiazole (1.00 g). The mixture was stirred at ambient temperature for four hours and evaporated in vacuo. The residue was triturated with acetone to give 1-[(2R, 6R)-3,5-dihydroxy-6-hydroxymethyl-4-(1,3,4-thiadiazol-2-yl)morpholin-2-yl]-uracil (3.0 g).
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11].[H-].[Na+].FC(F)(F)S(O[CH2:20][C:21]([F:24])([F:23])[F:22])(=O)=O>CN(C)C=O>[F:22][C:21]([F:24])([F:23])[CH2:20][N:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[C:2]1[CH:10]=[O:11]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: O=Cc1cc2cccnc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=Cc1cc2cccnc2n1CC(F)(F)F
Temperature: 0 °C
Reaction time: 1 h
Yield: 92.5 %

Procedure:
1H-Pyrrolo[2,3-b]pyridine-2-carbaldehyde (1.8 g, 12.32 mmol) was added to a solution of sodium hydride (0.54 g, 13.55 mmol) in N,N-dimethylformamide (50 mL) at rt under nitrogen. The reaction mixture was allowed to stir for 1 h before the reaction mixture was cooled to 0° C. and 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.04 ml, 14.78 mmol available, for example, from Sigma Aldrich) was added dropwise. The reaction mixture was stirred for 1 h at 0° C. and for 14 h at rt under nitrogen. The reaction was quenched by addition of water (150 mL). After addition of Et2O (150 mL), the layers were separated. The aqueous layer was further extracted with Et2O (3×150 mL) and the combined organic layers were washed with H2O. The combined water layers were extracted with Et2O (150 mL). The organic layers collected were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was loaded in dichloromethane on two 100 g SNAP silica cartridge and purified by SP4, eluting with 0-30% ethyl acetate/cyclohexane gradient. The appropriate fractions were combined and evaporated under reduced pressure to give the required product 1-(2,2,2-trifluoroethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2.6 g, 11.39 mmol, 93% yield) as a white solid.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[Br:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]([OH:31])[CH2:21][CH2:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:16][CH:15]=1.C(N(CC)CC)C>C(Cl)Cl>[Br:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20](=[O:31])[CH2:21][CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:16][CH:15]=1
Reactant: OC(CCCCc1ccccc1)c1ccc(CCBr)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=C(CCCCc1ccccc1)c1ccc(CCBr)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 88.4 %

Procedure:
To a solution of dimethyl sulfoxide (12. 7 ml) in methylene chloride (320 ml) was added a solution of oxalyl chloride (7.7 ml) in methylene chloride (320 ml) over 10 minutes under a nitrogen atmosphere at −68 to −65° C., and the mixture was stirred at the said temperature for 10 minutes. Then, a solution of 1-[4-(2-bromoethyl)phenyl]-5-phenylpentan-1-ol (20.7 g) in methylene chloride (80 ml) was added thereto at −68 to −65° C. over 20 minutes and the mixture was stirred at the said temperature for an hour. Triethylamine (41.6 ml) was further added thereto over 10 minutes at the said temperature and the mixture was stirred for 2.5 hours while raising the temperature of the mixture to 0° C. gradually. The reaction mixture was washed with water (100 ml) and saturated brine (100 ml), dried over anhydrous sodium sulfate and the solvent was distilled away under reduced pressure to give a brown oily substance. The obtained brown oily substance was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=20:1) to give 1-[4-(2-bromoethyl)phenyl]-5-phenylpentan-1-one (18.2 g) as a yellow oily substance.