Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.FC(F)(F)S(O[C:22]1[CH:35]=[C:34]2[C:25]([O:26][C:27]3[CH:28]=[CH:29][C:30]([C:41]4[CH:42]=[N:43][CH:44]=[N:45][CH:46]=4)=[CH:31][C:32]=3[C@:33]32[CH2:39][O:38][C:37]([NH2:40])=[N:36]3)=[CH:24][C:23]=1[F:47])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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>[O:1]1[CH2:2][CH:3]=[C:4]([C:22]2[C:23]([F:47])=[CH:24][C:25]3[O:26][C:27]4[C:32](=[CH:31][C:30]([C:41]5[CH:46]=[N:45][CH:44]=[N:43][CH:42]=5)=[CH:29][CH:28]=4)[C@@:33]4([CH2:39][O:38][C:37]([NH2:40])=[N:36]4)[C:34]=3[CH:35]=2)[CH2:5][CH2:6]1
Reactant: CC1(C)OB(C2=CCOCC2)OC1(C)C
Reactant: NC1=N[C@@]2(CO1)c1cc(-c3cncnc3)ccc1Oc1cc(F)c(OS(=O)(=O)C(F)(F)F)cc12
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: CN(C)C=O
Solvent: O
Product: NC1=N[C@@]2(CO1)c1cc(-c3cncnc3)ccc1Oc1cc(F)c(C3=CCOCC3)cc12
Temperature: 85 °C

Procedure:
A 0.5-2 ml microwave vial was charged with tetrakis(triphenylphosphine)palladium(0) (27.9 mg, 0.024 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (86 mg, 0.411 mmol). A solution of (S)-2-amino-6′-fluoro-2′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthene]-7′-yl trifluoromethanesulfonate (120 mg, 0.242 mmol) in DMF (1612 μL) was added followed by sodium carbonate (2M solution) (363 μL, 0.725 mmol). The vial was sealed and heated in microwave reactor at 85° C. for 1 hr. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with water, brine, filtered through celite and concentrated to leve brown oil. The crude material was purified by silica gel chromatography on 12 g RediSep column using (15-60% DCM/MeOH/NH4OH 90:10:1 in DCM) to afford (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-3′-fluoro-7′-(pyrimidin-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine. Found MS: MH+=431.
Reaction SMILES: C(C1C=C2C(=C(C(C)C)C=1)N=CN(/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20])C2=O)(C)C.[CH2:23]([N:25]([CH2:29][CH3:30])[CH2:26][CH2:27]Cl)[CH3:24].C(O)(C)C.[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]\[C:38]([OH:40])=[O:39]>CCOCC.C(Cl)Cl>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]\[C:38]([OH:40])=[O:39].[C:19]([O:21][CH2:27][CH2:26][N:25]([CH2:23][CH3:24])[CH2:29][CH3:30])(=[O:20])[CH:18]=[CH2:17]
Reactant: CCN(CC)CCCl
Reactant: CC(C)c1cc(C(C)C)c2ncn(/C=C/C(=O)O)c(=O)c2c1
Agent: O=C(O)/C=C\C(=O)O
Solvent: CC(C)O
Solvent: CCOCC
Solvent: ClCCl
Product: C=CC(=O)OCCN(CC)CC

Procedure:
A suspension of 1.42 g. of trans-3-(6,8-diisopropyl-4-oxo-4H-quinazolin-3-yl)-2-propenoic acid and 1.36 g. of 2-(diethylamino)ethyl chloride in 150 ml. of isopropyl alcohol was stirred and heated at reflux for 16 hours. The reaction mixture was concentrated in vacuo and then partitioned between methylene chloride and saturated sodium bicarbonate solution. The methylene chloride layer was dried (sodium sulfate) and concentrated in vacuo to yield 1.20 g. of an oil. The oil was dissolved in 5 ml. of methylene chloride and treated with a solution of 0.35 g. of maleic acid in 25 ml. of ether. After concentration in vacuo, the residue was crystallized from isopropyl alcohol-ether to give trans-3-(6,8-diisopropyl-4-oxo-4H-quinazolin)-3-yl)-2-propenoic acid, 2-(diethylamino)ethyl ester maleate, mp 81°-83°.
Reaction SMILES: Cl[CH2:2][C:3]([CH3:31])([CH3:30])[C:4]([N:6]([C@H:16]1[CH2:21][CH2:20][C@H:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)=[O:5].[C:32]([O-:35])([O-])=[O:33].[K+].[K+].[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>CN(C=O)C>[N:38]1([C:32]([O:35][CH2:2][C:3]([CH3:31])([CH3:30])[C:4]([N:6]([C@H:16]2[CH2:21][CH2:20][C@H:19]([NH:22][C:23]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:29])[CH2:18][CH2:17]2)[CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[O:5])=[O:33])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1
Reactant: O=C([O-])[O-]
Reactant: COc1ccc(CN(C(=O)C(C)(C)CCl)[C@H]2CC[C@H](NC(=O)OC(C)(C)C)CC2)cc1
Reactant: C1COCCN1
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(CN(C(=O)C(C)(C)COC(=O)N2CCOCC2)[C@H]2CC[C@H](NC(=O)OC(C)(C)C)CC2)cc1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
A stirred solution of 15B (75 mg, 0.166 mmol) in DMF (1 mL) was treated with K2CO3 (68.6 mg, 0.497 mmol), and morpholine (0.058 mL, 0.662 mmol). The reaction mixture was stirred at 90° C. overnight. The reaction mixture was concentrated and the residue was redissolved into small amount of MeOH, purified by preparative HPLC, (PHENOMENEX® Axia Luna 5 micron 30×100 mm, MeOH-water-TFA gradient). Concentration of the appropriate fractions provided 33 mg (37%) of 15C. MS (ES): m/z=548.2 [M+H]+.
Reaction SMILES: C[O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][N:13](C)[C:14]([NH:16][CH:17]2[CH:24]3[CH2:25][CH:20]4[CH2:21][CH:22]([CH2:26][CH:18]2[CH2:19]4)[CH2:23]3)=[O:15])=[CH:6][CH:5]=1.[OH-].[Na+].O.[CH2:32]1COCC1>>[CH:18]12[CH2:26][CH:22]3[CH2:21][CH:20]([CH2:25][CH:24]([CH2:23]3)[CH:17]1[N:16]([CH3:32])[C:14](=[O:15])[NH:13][CH2:12][CH2:11][O:10][C:7]1[CH:6]=[CH:5][C:4]([C:3]([OH:2])=[O:28])=[CH:9][CH:8]=1)[CH2:19]2
Reactant: C1CCOC1
Reactant: COC(=O)c1ccc(OCCN(C)C(=O)NC2C3CC4CC(C3)CC2C4)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CN(C(=O)NCCOc1ccc(C(=O)O)cc1)C1C2CC3CC(C2)CC1C3
Reaction time: 8 h

Procedure:
A solution of 4-[2-(3-Adamantan-2-yl-1-methyl-ureido)-ethoxy]-benzoic acid methyl ester 562 mg (1.45 mmol), NaOH 1 N 3 ml in THF 5 ml was stirred at RT overnight. Then NaOH 1 N 4 ml was added and the reaction mixture stirred overnight. Water was added and the mixture acidified until pH=2.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:27]([OH:28])[C@@H:26]([CH2:29][OH:30])[O:25][C@H:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])[C@@H:10]1[O:31][C@H:32]1[O:61][C@H:60]([CH2:62][O:63][CH2:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[C@@H:51]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C@H:42]([O:43][CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C@H:33]1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:71]([O-])(=[O:74])(=[O:73])[CH3:72]>>[CH2:1]([O:8][C@H:9]1[C@H:27]([OH:28])[C@@H:26]([CH2:29][O:30][S:71]([CH3:72])(=[O:74])=[O:73])[O:25][C@H:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])[C@@H:10]1[O:31][C@H:32]1[O:61][C@H:60]([CH2:62][O:63][CH2:64][C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=2)[C@@H:51]([O:52][CH2:53][C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[C@H:42]([O:43][CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C@H:33]1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)[O-]
Reactant: COC(=O)CCCCCCCCO[C@H]1O[C@H](CO)[C@@H](O)[C@H](OCc2ccccc2)[C@H]1O[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Product: COC(=O)CCCCCCCCO[C@H]1O[C@H](COS(C)(=O)=O)[C@@H](O)[C@H](OCc2ccccc2)[C@H]1O[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Yield: 79.1 %

Procedure:
Compound 38 (450 mg, 0.47 mmol) was converted into its 6-O-methane sulfonyl derivative exactly as described for the preparation of 10 to provide 39 (385 mg, 79.1%) as a syrup after chromatography on silica gel using (hexane:ethyl acetate; 2:1) as eluant; ›α!D +36.1° (c 0.95, chloroform). 1H-n.m.r. (CDCl3): δ 4.99(d, 1H, J1',2' 3.8 Hz, H-1'), 4.96(d, 1H, J1,2 3.8 Hz, H-1), 3.58(s, 3H, OCH3), 2.93(s, 3H, CH3SO2), 2.39(d, 1H, J 3.2 Hz, OH, D2O exchangeable), 2.21(t, 2H, J 7.5 Hz, CH2COO).
Reaction SMILES: O[CH:2]([OH:22])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:13]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:16][CH:17]=2)=[CH:7][CH:6]=1)=[O:4].[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=1.[CH2:33](O)[CH3:34].C1(C)C=CC=CC=1>CCOCC>[CH2:33]([O:22][CH:2]([NH:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][CH:25]=1)[C:3](=[O:4])[C:5]1[CH:6]=[CH:7][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=2)=[CH:9][CH:10]=1)[CH3:34]
Reactant: Nc1ccc(C(=O)O)cc1
Reactant: O=C(c1ccc(Oc2cccc(C(F)(F)F)c2)cc1)C(O)O
Reactant: CCO
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CCOC(Nc1ccc(C(=O)O)cc1)C(=O)c1ccc(Oc2cccc(C(F)(F)F)c2)cc1
Temperature: 0 °C

Procedure:
A mixture of 5.62 g of 2,2-dihydroxy-4'-(α,α,α-trifluoro-m-tolyloxy)acetophenone, 2.47 g of p-aminobenzoic acid and 100 ml of ethanol was refluxed for 30 minutes and then 50 ml of toluene were added. The mixture was evaporated to dryness and the refluxing with ethanol and toluene repeated twice. Then the ethanol was evaporated giving a residue which was dissolved in 150 ml of ether, 75 ml of petroleum ether was added and the mixture cooled to 0° C., giving the desired product as an off-white powder, mp 109°-122° C. (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:21])[CH2:9][CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)=[C:4]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:44]1[CH:48]=[CH:47][N:46]=[C:45]1[C:49](Cl)=O>CN(C=O)C>[CH3:18][O:17][C:15](=[O:16])[C:14]1[CH:19]=[CH:20][C:11]([CH2:10][C:9]2[C:8](=[O:21])[C:5]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:49]=2[C:45]2[O:44][CH:48]=[CH:47][N:46]=2)=[CH:12][CH:13]=1
Reactant: O=C(Cl)c1ncco1
Reactant: COC(=O)c1ccc(CCC(=O)c2ccc(Cl)cc2Nc2ccccc2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Cc2c(-c3ncco3)n(-c3ccccc3)c3cc(Cl)ccc3c2=O)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 2.6 %

Procedure:
Separately, in a 100 mL round-bottomed flask, methyl 4-(3-(4-chloro-2-(phenylamino)phenyl)-3-oxopropyl)benzoate (898 mg, 2.28 mmol) was combined with THF to give a yellow solution. A 1.0 M solution of NaHMDS in THF (5.7 ml, 5.7 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes. A heterogeneous mixture of oxazole-2-carbonyl chloride from above, THF (5 mL), DMF (500 μL) was added dropwise to the reaction mixture. The mixture was stirred at room temperature overnight. The reaction flask was cooled to 0° C., then the reaction was quenched with water. The resulting heterogeneous mixture was extracted with ethyl acetate, and the organic phase was dried over MgSO4, filtered, then concentrated. The crude product was dissolved in methylene chloride, then concentrated over silica gel. The silica gel supported crude product was loaded onto a 80 gram analogix column. Flash chromatography (15% EtOAc-hexanes→55% EtOAc-hexanes) provided 4-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester (28 mg, 2.6%) as a light yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[CH:11]=[CH:10]2)=[O:4].C(O[CH2:28][C:29](=[CH2:35])[CH2:30][Si](C)(C)C)(=O)C.P(OC(C)C)(OC(C)C)OC(C)C>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:8]=[C:9]2[C:14]=1[O:13][C:12](=[O:15])[CH:11]1[CH2:30][C:29](=[CH2:28])[CH2:35][CH:10]21)=[O:4]
Reactant: C=C(COC(C)=O)C[Si](C)(C)C
Reactant: COC(=O)c1cc(OCc2ccccc2)cc2ccc(=O)oc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)OP(OC(C)C)OC(C)C
Solvent: C1CCOC1
Product: C=C1CC2C(=O)Oc3c(C(=O)OC)cc(OCc4ccccc4)cc3C2C1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a solution of preparation 4 (198 mg, 0.64 mmol) and Pd(OAc)2 (17 mg, 0.076 mmol) in 4 mL THF add 2-(acetoxymethyl)allyl-trimethylsilane (0.163 mL, 0.122 mmol) followed by triisopropyl phosphite (0.12 mL, 0.49 mmol). After stirring at 60° C. overnight, cool the solution to room temperature, concentrate under reduced pressure, and dilute with EtOAc. Wash the solution with saturated aqueous sodium bicarbonate and brine. Dry over Na2SO4, and then concentrate to an oil. Purify the material by silica gel chromatography (10 g, 10 to 30% EtOAc/Hex over 30 min at 35 mL/min) to give 80 mg (0.208 mol, 63%) of preparation 6 and 30 mg (0.091 mmol, 27%) of recovered starting material. 1H NMR (400 MHz, CDCl3) δ 7.48-7.36 (m, 6H), 7.01 (d, 1H, J=3.1 Hz), 5.10 (s, 2H), 5.01 (m, 2H), 3.97 (s, 3H), 3.43 (dt, 1H, J=7.5, 3.1 Hz), 3.21-3.10 (m, 2H), 2.86-2.74 (m, 2H), 2.43 (m, 1H).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][NH2:20])=[CH:15][CH:14]=1.[CH:31](N(CC)C(C)C)([CH3:33])[CH3:32].C(Br)C=C>C(Cl)Cl>[CH2:33]([NH:20][CH2:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:11]([CH2:10][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH:21]2[C:30]3[N:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH2:24][CH2:23][CH2:22]2)=[CH:18][CH:17]=1)[CH:31]=[CH2:32]
Reactant: CCN(C(C)C)C(C)C
Reactant: NCc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Solvent: ClCCl
Solvent: C=CCBr
Product: C=CCNCc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1

Procedure:
To a solution of N′-(1H-benzimidazol-2-ylmethyl)-N′-(5,6,7,8-tetrahydro-8-quinolinyl)-1,4-benzenedimethanamine (200 mg, 0.39 mmol) in CH2Cl2 (˜0.4 mL) was added N,N-diisopropylethylamine (90 μL, 0.52 mmol). Allyl bromide (35 μL, 0.40 mmol) was dissolved in CH2Cl2 (˜9.6 mL) and added to the amine mixture at a rate of 5.5 mL/hour. The resultant mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with CH2Cl2 (50 mL) and washed consecutively with H2O (5 mL), saturated aqueous NaHCO3 (5 mL) and saturated aqueous NaCl (5 mL). The aqueous layer was extracted with CH2Cl2 (20 mL) and the combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. Purification by column chromatography on silica gel (200:1:1 followed by 100:1:1—EtOAc:MeOH:NH4OH) followed by radial chromatography on silica gel (250:1:1—EtOAc:MeOH:NH4OH) afforded AMD9725 (36 mg, 21%) as a light yellow foam. 1H NMR (CDCl3) δ 1.56–1.75 (m, 1H), 1.97–2.08 (m, 2H), 2.24–2.31 (m, 1H), 2.65–2.77 (m, 1H), 2.77–2.91 (m, 1H), 3.21 (d, 2H, J=5.7 Hz), 3.69 (s, 2H), 3.73 (s, 2H), 3.97 (d, 1H, J=16.8 Hz), 4.04–4.16 (m, 1H), 4.17 (d, 1H, J=16.8 Hz), 5.07 (d, 1H, J=9.9 Hz), 5.15 (dd, 1H, J=17.1, 1.2 Hz), 5.88 (ddt, 1H, J=17.1, 10.5, 6.0 Hz), 7.10–7.19 (m, 5H), 7.35 (d, 2H, J=7.8 Hz), 7.42 (d, 1H, J=7.5 Hz), 7.45–7.57 (m, 1H), 7.58–7.68 (m, 1H), 8.69 (d, 1H, J=4.2 Hz); 13C NMR (CDCl3) δ 20.83, 22.89, 28.67, 47.95, 51.11, 52.33, 53.17, 59.68, 110.37, 115.39, 118.11, 120.91, 121.66, 127.59, 128.07, 134.13, 136.17, 136.60, 137.48, 138.56, 146.38, 155.80, 156.94. ES-MS m/z 438.3 (M+H). Anal. Calcd. for C28H31N5.0.8H2O: C, 74.40; H, 7.27; N, 15.49. Found: C, 74.36; H, 7.25; N, 15.31.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([C:26]3[C:34]4[C:29](=[CH:30][C:31](Br)=[CH:32][CH:33]=4)[N:28]([CH3:36])[CH:27]=3)[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=3[O:24][CH3:25])(=[O:16])=[O:15])=[O:12])=[CH:9][C:4]=2[O:3][CH2:2]1.[CH:37]([O:39]CC)=[CH2:38].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:37]([C:31]1[CH:30]=[C:29]2[C:34]([C:26]([CH:10]([C:8]3[CH:7]=[CH:6][C:5]4[O:1][CH2:2][O:3][C:4]=4[CH:9]=3)[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=3[O:24][CH3:25])(=[O:16])=[O:15])=[O:12])=[CH:27][N:28]2[CH3:36])=[CH:33][CH:32]=1)(=[O:39])[CH3:38]
Reactant: C=COCC
Reactant: COc1cc(C)ccc1S(=O)(=O)NC(=O)C(c1ccc2c(c1)OCO2)c1cn(C)c2cc(Br)ccc12
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COc1cc(C)ccc1S(=O)(=O)NC(=O)C(c1ccc2c(c1)OCO2)c1cn(C)c2cc(C(C)=O)ccc12
Reaction time: 0.75 h

Procedure:
A mixture of 3-{1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-6-bromo-1-methyl-1H-indole (from Example 85, 300 mg, 0.53 mmol), ethyl vinyl ether (0.063 ml), palladium(II)acetate (6 mg), tri-o-tolylphosphine (13 mg) and triethylamine (0.1 ml) in acetonitrile (5 ml) was heated at reflux for 18 hours under a nitrogen atmosphere. After cooling, the solvent was evaporated in vacuo and the residue was stirred with 2N hydrochloric acid (˜6 ml) for 45 minutes. The mixture was twice extracted with ethyl acetate, and then washed with water, and brine, The organic layer was dried (magnesium sulphate) and the solvents were evaporated in vacuo. The residue was flash chromatographed using a gradient elution of a mixture of 90% hexane and 10% ethyl acetate, through to 40% hexane and 60% ethyl acetate, to give the title compound (80 mg).
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([F:9])[C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[CH2:11]([O:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1)[CH2:12][CH3:13]>>[F:10][C:4]1[CH:3]=[C:2]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH2:11][CH2:12][CH3:13])[CH:20]=2)[CH:8]=[C:7]([F:9])[C:5]=1[NH2:6]
Reactant: CCCOc1cccc(B(O)O)c1
Reactant: Nc1c(F)cc(Br)cc1F
Product: CCCOc1cccc(-c2cc(F)c(N)c(F)c2)c1
Yield: 47.5 %

Procedure:
The title compound (0.3 g) was prepared from 4-Bromo-2,6-difluoro aniline (0.5 g, 2.4 mmol) and 3-propoxyphenylboronic acid (0.337 g, 3.1 mmol) as a red liquid. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): 7.30-7.24 (m, 3H), 7.18-7.10 (m, 2H), 6.86-6.80 (m, 1H), 5.31 (s, 2H), 3.97 (t, J 6.5, 2H), 1.75-1.65 (m, 2H), 0.98 (t, J 7.4, 3H).
Reaction SMILES: C[Si](C)(C)N[Si](C)(C)C.[Na].C1COCC1.[Cl:16][C:17]1[CH:25]=[CH:24][C:20]2[O:21][CH2:22][O:23][C:19]=2[C:18]=1[NH2:26].Cl[C:28]1[C:33]([C:34]#[N:35])=[CH:32][N:31]=[C:30]2[N:36]=[C:37]([S:39][CH3:40])[S:38][C:29]=12>CN(C=O)C.O>[Cl:16][C:17]1[CH:25]=[CH:24][C:20]2[O:21][CH2:22][O:23][C:19]=2[C:18]=1[NH:26][C:28]1[C:33]([C:34]#[N:35])=[CH:32][N:31]=[C:30]2[N:36]=[C:37]([S:39][CH3:40])[S:38][C:29]=12
Reactant: Nc1c(Cl)ccc2c1OCO2
Reactant: CSc1nc2ncc(C#N)c(Cl)c2s1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: [Na]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: CSc1nc2ncc(C#N)c(Nc3c(Cl)ccc4c3OCO4)c2s1
Reaction time: 0.25 h

Procedure:
1M sodium hexamethyldisilazane in THF (1.42 mL, 1.42 mmol) was added to 5-chloro-benzo[1,3]dioxol-4-ylamine Compound 31a (as described in PCT Application WO03/008409) (221 mg, 1.29 mmol) in DMF at 0° C. and the mixture was stirred for 15 min. 7-chloro-2-methylsulfanyl-thiazolo[4,5-b]pyridine-6-carbonitrile Compound 1g (312 mg, 1.29 mmol) in DMF (1 mL) was added and the reaction mixture stirred for an additional 2 hr at ambient temperature. The mixture was then diluted with water and filtered through Celite 545 to form a plug. The celite plug was rinsed with EtOAc and the organic layer was isolated and washed with brine. The organic layer was dried over MgSO4, then filtered and evaporated onto silica gel. Isolation by flash chromatography (eluted with a 20 to 40% EtOAc/hexane gradient) gave 7-(5-chloro-benzo[1,3]dioxol-4-ylamino)-2-methylsulfanyl-thiazolo[4,5-b]pyridine-6-carbonitrile Compound 31b (30 mg) as a yellow oil. MS 377, 379 (MH+).
Reaction SMILES: [CH2:1]1[O:12][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH2:13]([NH2:17])[CH2:14][CH2:15][NH2:16]>CO>[CH2:13]([NH:17][CH2:1][CH:2]([OH:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:14][CH2:15][NH:16][CH2:1][CH:2]([OH:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCCCCCC1CO1
Reactant: NCCCN
Solvent: CO
Product: CCCCCCCCCC(O)CNCCCNCC(O)CCCCCCCCC

Procedure:
In a manner similar to that of Example 1, condensation of 1-undecene oxide (104.6 g.) and 1,3-propanediamine (22.7 g.) and two recrystallizations of the resulting product from methanol gave N,N'-(1,3-propylene)-bis[2-hydroxyundecylamine] (I: R= CH3 (CH2)8, R' = H, X= (CH2)3, Z= H) (29.0 g., m.p. 94.0°-103.0° C.).
Reaction SMILES: [CH3:1][S:2][C:3]1[O:7][C:6]([C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[N:5][N:4]=1.Cl[C:17]1[N:26]=[C:25]([NH2:27])[C:24]2[C:19](=[CH:20][C:21]([O:30][CH3:31])=[C:22]([O:28][CH3:29])[CH:23]=2)[N:18]=1>C(O)CC(C)C>[NH2:27][C:25]1[C:24]2[C:19](=[CH:20][C:21]([O:30][CH3:31])=[C:22]([O:28][CH3:29])[CH:23]=2)[N:18]=[C:17]([N:13]2[CH2:14][CH2:15][CH:10]([C:8]([C:6]3[O:7][C:3]([S:2][CH3:1])=[N:4][N:5]=3)=[O:9])[CH2:11][CH2:12]2)[N:26]=1
Reactant: CSc1nnc(C(=O)C2CCNCC2)o1
Reactant: COc1cc2nc(Cl)nc(N)c2cc1OC
Solvent: CC(C)CCO
Product: COc1cc2nc(N3CCC(C(=O)c4nnc(SC)o4)CC3)nc(N)c2cc1OC

Procedure:
2.13 g of 4-(5-methylthio-1,3,4-oxadiazole-2-carbonyl)-piperidine and 2.4 g of 2-chloro-4-amino-6,7-dimethoxy-quinazoline in 50 cm3 of isoamyl alcohol are heated under reflux for 8 hours with stirring. After cooling and concentration, 3.9 g of product are isolated, which are purified by recrystallisation from ethanol.
Reaction SMILES: [O:1]=[C:2]1[CH2:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH2:5][C:4]2[CH:13]=[C:14]([CH2:17][C:18]([OH:20])=[O:19])[CH:15]=[CH:16][C:3]1=2.[CH2:21](O)[CH3:22]>Cl>[O:1]=[C:2]1[CH2:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH2:5][C:4]2[CH:13]=[C:14]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:15]=[CH:16][C:3]1=2
Reactant: O=C(O)Cc1ccc2c(c1)Cc1ccccc1CC2=O
Reactant: CCO
Agent: Cl
Product: CCOC(=O)Cc1ccc2c(c1)Cc1ccccc1CC2=O

Procedure:
In 3 ml of a 12% ethanol solution of hydrogen chloride was dissolved 0.14 g of 10,11-dihydro-11-oxo-5H-dibenzo[a,d]cycloheptene-3-acetic acid obtained in Example 3. The solution was heated under reflux for 30 minutes with stirring. After the reaction, the reaction mixture was cooled, and the solvent was distilled off. Water was added to the residue, and the mixture was extracted with ether. The ethereal layer was washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. Then, the ether was distilled off. The residue was chromatographed on a silica gel column using benzene as an eluent. From the eluate, 0.12 g of ethyl 10,11-dihydro-11-oxo-5H-dibenzo[a,d]cycloheptene-3-acetate was obtained as a slightly yellow oily substance.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([CH2:20][CH2:21][CH2:22][OH:23])[CH:19]=2)=[CH:11][C:3]=1[C:4]([N:6](CC)[CH2:7][CH3:8])=[O:5].NC1C=CC(Br)=CC=1C(NCC)=O>>[NH2:1][C:2]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([CH2:20][CH2:21][CH2:22][OH:23])[CH:19]=2)=[CH:11][C:3]=1[C:4]([NH:6][CH2:7][CH3:8])=[O:5]
Reactant: CCN(CC)C(=O)c1cc(-c2cnn(CCCO)c2)ccc1N
Agent: CCNC(=O)c1cc(Br)ccc1N
Product: CCNC(=O)c1cc(-c2cnn(CCCO)c2)ccc1N
Yield: 37 %

Procedure:
Prepared analogously to Compound 3C replacing Compound 3D with 2-amino-5-bromo-N-ethylbenzamide (Compound 9D, 1.40 g, 5.77 mmol) to afford 729 mg of the title compound (37%). 1H NMR (400 MHz, CD3OD) δ 7.87 (s, 1H), 7.76 (d, J=0.5 Hz, 1H), 7.63 (d, J=2.0 Hz, 1H), 7.34-7.41 (m, 1H), 6.77 (d, J=8.3 Hz, 1H), 4.25 (t, J=6.9 Hz, 2H), 3.54 (t, J=6.2 Hz, 2H), 3.38 (q, J=7.2 Hz, 2H), 2.06 (quin, J=6.6 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H). MS (ESI): m/z 289.32 [M+H]+. UPLC: tR=0.63 min (UPLC-SQD: analytical—2 min).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([S:7]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=2)(=[O:9])=[O:8])[CH:2]=1.S(Cl)([Cl:22])=O>CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([S:7]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([Cl:22])=[O:16])=[CH:13][CH:12]=2)(=[O:9])=[O:8])[CH:2]=1
Reactant: O=C(O)c1ccc(NS(=O)(=O)c2cccnc2)cc1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(NS(=O)(=O)c2cccnc2)cc1

Procedure:
Into a 500 ml-flask fitted with a mechanical stirrer and a condenser were introduced 26 g (0.093 mol) of 4-(3-pyridylsulfonamido)-benzoic acid and 180 ml of thionyl chloride, after which a few drops of dimethylformamide were added as catalyst. The mixture was progressively heated to boiling, which was maintained for three hours.