Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH:8]=O)[CH2:4][CH2:3]1.O1CCCC1.[NH:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[Cl-].[Na+].O>[F:1][C:2]1([F:10])[CH2:7][CH2:6][CH:5]([CH2:8][N:16]2[CH2:17][CH2:18][CH:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:20][CH2:21]2)[CH2:4][CH2:3]1
Reactant: O=CC1CCC(F)(F)CC1
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NC1CCN(CC2CCC(F)(F)CC2)CC1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 20.7 %

Procedure:
A mixture of the crude product of 4,4-difluorocyclohexane-1-carbaldehyde obtained in Example 2b (1.4 g) and tetrahydrofuran (100 ml) was cooled to 0° C., tert-butyl N-(piperidin-4-yl)carbamate (2.27 g, 11.3 mmol) was added thereto, followed by stirring for 20 minutes. Sodium triacetoxyborohydride (2.2 g, 10.4 mmol) was then added to the reaction mixture, which was stirred at mom temperature for eight hours. Brine was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane). The resulting residue was dissolved in ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution, and the solvent was then distilled off to give the title compound (650 mg, yield 20.7%).
Reaction SMILES: [O:1]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[CH:20]=[C:19]([NH:21][CH:22]3[CH2:26][CH2:25][NH:24][CH2:23]3)[N:18]=[CH:17][N:16]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38]>C1COCC1>[O:1]([C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15]2[N:16]=[CH:17][N:18]=[C:19]([NH:21][CH:22]3[CH2:26][CH2:25][N:24]([C:36](=[O:39])[CH:37]=[CH2:38])[CH2:23]3)[CH:20]=2)=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CC(=O)Cl
Reactant: c1ccc(Oc2ccc(Nc3cc(NC4CCNC4)ncn3)cc2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: C=CC(=O)N1CCC(Nc2cc(Nc3ccc(Oc4ccccc4)cc3)ncn2)C1
Temperature: -60 °C
Reaction time: 0.08 h

Procedure:
To a stirred solution of N4-(4-phenoxyphenyl)-N6-(pyrrolidin-3-yl)pyrimidine-4,6-diamine (0.13 g, 0.3 mmol) in THF (1.5 mL) at −60° C. were added DIPEA (0.07 g, 0.5 mmol) and acryloyl chloride (1 M solution in THF, 0.3 mL, 0.3 mmol), and the reaction mixture was stirred at −60° C. for 5 min. The reaction mixture was quenched by adding water and it was extracted with EtOAc (2×5 mL). The combined EtOAc extract was washed with brine (3 mL), was dried over Na2SO4 and was concentrated under reduced pressure. The residue obtained was purified by column chromatography (SiO2, 230-400, chloroform/methanol:98/2) to give 1-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyrrolidin-1-yl)prop-2-en-1-one (I-85) as a light green solid. 1H NMR (DMSO-d6) δ ppm: 1.83-1.86 & 1.90-1.94 (m, 1H), 2.07-3.0 & 2.16-2.20 (m, 1H), 3.38-3.86 (m, 4H), 4.2-4.75 & 4.35-4.5 (bs, 1H), 5.65 (dt, J=2 & 10 Hz, 1H), 5.78 (d, J=3.6 Hz, 1H), 6.11 & 6.15 (dd, J=2.4 & 7.0 Hz & dd, J=2.4 & 7.2 Hz, 1H), 6.51-6.64 (m, together 1H), 6.93-7.00 (m, 4H), 7.07-7.18 (m, 2H), 7.36 (t, J=8 Hz, 2H), 7.51 (d, J=8 Hz, 2H), 8.12 (s, 1H), 8.93 (s, 1H); LCMS: m/e 401.8 (M+1).
Reaction SMILES: C(O)(=O)C.[OH:5][CH2:6][C:7]1[CH:8]=[C:9]([CH:15]([NH:28][C:29]2[CH:37]=[CH:36][C:32]([C:33]([NH2:35])=[NH:34])=[CH:31][CH:30]=2)[C:16]2[NH:20][C:19](=[O:21])[N:18]([C:22]3[N:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:17]=2)[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1.[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>CS(C)=O>[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41].[OH:5][CH2:6][C:7]1[CH:8]=[C:9]([C@H:15]([NH:28][C:29]2[CH:30]=[CH:31][C:32]([C:33]([NH2:35])=[NH:34])=[CH:36][CH:37]=2)[C:16]2[NH:20][C:19](=[O:21])[N:18]([C:22]3[N:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:17]=2)[CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1
Reactant: COc1cc(CO)cc(C(Nc2ccc(C(=N)N)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c1
Solvent: CS(C)=O
Solvent: O=C(O)C(F)(F)F
Solvent: CC(=O)O
Product: COc1cc(CO)cc([C@H](Nc2ccc(C(=N)N)cc2)c2nn(-c3ncccn3)c(=O)[nH]2)c1

Procedure:
After adding trifluoroacetic acid to a suspension of 28.5 mg of 4-{[(3-hydroxymethyl-5-methoxyphenyl)-(5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]triazol-3-yl)methyl]amino}benzamidine acetate in 2.85 ml of DMSO, the mixture was concentrated under reduced pressure. The residue was optically resolved using a SUMICHIRAL OA-2500 column, and the first fraction was obtained. This was dissolved in a trifluoroacetic acid:acetonitrile:water=1:50:50 mixed solvent and concentrated, and the first fraction (9.80 mg) of the title compound was obtained as a white solid.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:6]=[C:7]([C:15]([OH:17])=O)[C:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C:13]=2[CH:14]=1)([CH3:3])[CH3:2].C(Cl)(=O)C([Cl:21])=O>C(Cl)Cl.CN(C=O)C>[CH:1]([O:4][C:5]1[CH:6]=[C:7]([C:15]([Cl:21])=[O:17])[C:8]2[CH2:9][CH2:10][CH2:11][CH2:12][C:13]=2[CH:14]=1)([CH3:3])[CH3:2]
Reactant: CC(C)Oc1cc2c(c(C(=O)O)c1)CCCC2
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)Oc1cc2c(c(C(=O)Cl)c1)CCCC2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 3-(isopropoxy)-5,6,7,8-tetrahydro-1-naphthalenecarboxylic acid (0.318 g, 1.36 mmol) in DCM (5 mL) was added oxalyl chloride (0.15 mL, 1.70 mmol) and 2 drops of DMF. The mixture was stirred at room temperature for 3 h. The solvent was removed in vacuo and the 3-(isopropoxy)-5,6,7,8-tetrahydro-1-naphthalenecarbonyl chloride was used without purification.
Reaction SMILES: Cl[CH:2]([C:4]1[N:13]([CH3:14])[C:12]2[C:11](=[O:15])[N:9]([CH3:10])[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[N:5]=1)[CH3:3].[C:18]([O-:26])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1.[K+]>CN(C)C=O>[C:18]([O:26][CH:2]([C:4]1[N:13]([CH3:14])[C:12]2[C:11](=[O:15])[N:9]([CH3:10])[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[N:5]=1)[CH3:3])(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=1
Reactant: O=C([O-])c1cccnc1
Reactant: CC(Cl)c1nc2c(c(=O)n(C)c(=O)n2C)n1C
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(OC(=O)c1cccnc1)c1nc2c(c(=O)n(C)c(=O)n2C)n1C
Temperature: 100 °C
Reaction time: 1 h

Procedure:
2.57 g of 8-α-chloroethylcaffeine are dissolved in 25 ml of anhydrous dimethylformamide, to which 2.98 g of dry potassium nicotinate are added. The mixture is heated under shaking at 100° C for 1 hour, then filtered off and the filtrate evaporated under reduced pressure. The residue, after washing with water, gives 3.1 g of slightly crude product which is purified by crystallization from 95% ethanol : m.p. (EtOH) 160° C. The monohydrochloride melts at 200°-210° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](S(C)=O)[N:3]=1.Cl.[CH2:19]([O:26][C:27](=[O:32])[NH:28][CH2:29][CH2:30][NH2:31])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C1CCN2C(=NCCC2)CC1>COCCOC>[CH2:19]([O:26][C:27](=[O:32])[NH:28][CH2:29][CH2:30][NH:31][C:4]1[C:5]([C:13]#[N:14])=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:7]=[C:2]([NH2:1])[N:3]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1C#N
Reactant: NCCNC(=O)OCc1ccccc1
Agent: Cl
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(NCCNC(=O)OCc2ccccc2)nc(N)nc1-c1ccco1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, (2-amino-ethyl)-carbamic acid benzyl ester hydrochloride and DBU in DME. ES-MS m/e (%): 401 (M+Na+, 20), 379 (M+H+, 100).
Reaction SMILES: C1(S(O[CH:11]2[N:23]3[C:14](=[N:15][C:16]4[CH:17]=[C:18]([Br:25])[CH:19]=[CH:20][C:21]=4[C:22]3=[O:24])[CH2:13][CH2:12]2)(=O)=O)C=CC=CC=1.[C:26](=[O:29])([O-])[O-].[K+].[K+].[CH3:32]O>>[Br:25][C:18]1[CH:19]=[CH:20][C:21]2[C:22](=[O:24])[N:23]3[CH:11]([CH2:32][O:29][CH3:26])[CH2:12][CH2:13][C:14]3=[N:15][C:16]=2[CH:17]=1
Reactant: CO
Reactant: O=C([O-])[O-]
Reactant: O=c1c2ccc(Br)cc2nc2n1C(OS(=O)(=O)c1ccccc1)CC2
Agent: [K+]
Product: COCC1CCc2nc3cc(Br)ccc3c(=O)n21
Temperature: 25 °C

Procedure:
A solution of 6-bromo-9-oxo-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-yl benzenesulfonate (300 mg, 0.69 mmol) and potassium carbonate (290 mg, 2.1 mmol) in methanol (80 mL) was stirred at reflux for 2 h. After it was cooled to room temperature, the mixture was concentrated and purified by silica-gel chromatography to give the desired product. MS (ESI): 309, 311 (MH+).
Reaction SMILES: [CH:1]1([OH:12])[CH:6]([OH:7])[CH:5]([OH:8])[CH:4]([OH:9])[CH:3]([OH:10])[CH:2]1[OH:11].C(O)[C@H]1O[C@H]([O:20][CH:21]2[C@@H:26]([OH:27])[C@@H:25]([OH:28])[CH:24]([OH:29])[C@H:23]([OH:30])[C@H:22]2[OH:31])[C@H](O)[C@@H](O)[C@H]1O.[CH2:36]([OH:58])[C@H:37]1[O:42][C@H:41]([O:43][CH:44]2[C@@H:49]([OH:50])[C@H:48]([OH:51])[CH:47]([OH:52])[C@@H:46]([OH:53])[C@@H:45]2[OH:54])[C@H:40]([OH:55])[C@@H:39]([OH:56])[C@H:38]1[OH:57]>>[O:7]=[CH:6][C@@H:5]([C@H:4]([C@H:3]([C@@H:2]([CH2:1][OH:12])[OH:11])[OH:10])[OH:9])[OH:8].[CH:21]1([OH:20])[CH:22]([OH:31])[CH:23]([OH:30])[CH:24]([OH:29])[CH:25]([OH:28])[CH:26]1[OH:27].[CH2:36]([OH:58])[C@H:37]1[O:42][C@H:41]([O:43][CH:44]2[C@@H:45]([OH:54])[C@@H:46]([OH:53])[CH:47]([OH:52])[C@H:48]([OH:51])[C@H:49]2[OH:50])[C@H:40]([OH:55])[C@@H:39]([OH:56])[C@H:38]1[OH:57]
Reactant: OC[C@H]1O[C@H](OC2[C@@H](O)[C@H](O)C(O)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@H]1O
Agent: OC1C(O)C(O)C(O)C(O)C1O
Agent: OC[C@H]1O[C@H](OC2[C@@H](O)[C@@H](O)C(O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@H]1O
Product: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO

Procedure:
Results. Buckwheat bran was extracted with 50% EtOH, and the resulting extract chromatographed on carbon-Celite, 1:1 (w/w), to purify Fagopyritol A1. Fagopyritol B1 was also purified from the same sample for comparison. Per(pentafluoropropionates) of chiro-inositol from acid hydrolysis of Fagopyritol A1 and Fagopyritol B1 co-chromatographed on a chiral column with authentic D-chiro-inositol, but not with authentic L-chiro-inositol. Hydrolysis of Fagopyritol A1 and Fagopyritol B1 produced D-galactose and D-chiro-inositol in mole ratios of 1.01:1.00 for Fagopyritol A1 and 1.03:1.00 for Fagopyritol B11. Free D-chiro-inositol was obtained by acid hydrolysis of a mixture of Fagopyritol A1 and Fagopyritol B1 followed by purification on a carbon-Celite column. Fagopyritol A1 and Fagopyritol B1 were hydrolyzed by β-D-galactosidase, but not by β-D-galactosidase, demonstrating an α-D-galactopyranosyl linkage.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[N:11]=[CH:12][N:13]([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH:25](C)[C@H:24](O)[O:23][C:22]3=[O:28])=[CH:17][C:16]=2[F:29])[CH:14]=1)(C(C)(C)C)(C)C.C(O[C:35]([NH:37][C:38]1[CH:42]=[CH:41][O:40][N:39]=1)=O)(C)(C)C.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[O:40]1[CH:41]=[CH:42][C:38]([NH:37][CH2:35][C@@H:24]2[O:23][C:22](=[O:28])[N:21]([C:18]3[CH:19]=[CH:20][C:15]([N:13]4[CH:14]=[C:10]([CH2:9][OH:8])[N:11]=[CH:12]4)=[C:16]([F:29])[CH:17]=3)[CH2:25]2)=[N:39]1
Reactant: CC1[C@H](O)OC(=O)N1c1ccc(-n2cnc(CO[Si](C)(C)C(C)(C)C)c2)c(F)c1
Reactant: CC(C)(C)OC(=O)Nc1ccon1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: O=C1O[C@@H](CNc2ccon2)CN1c1ccc(-n2cnc(CO)c2)c(F)c1
Reaction time: 18 h
Yield: 13.9 %

Procedure:
3-(4-(4-t-Butyldimethylsilyloxymethylimidazol-1-yl)-3-fluorophenyl)-5(R)-hydroxy-methyloxazolidin-2-one (842 mg, 2 mM, see WO 97-31917) and 3-(t-butoxycarbonyl-amino)isoxazole (405 mg, 2.2 mM) were suspended by stirring in dry tetrahydrofuran (15 ml) under nitrogen in an ice-bath. Tributylphosphine (444 mg, 2.2 mM) followed by 1,1′-(azo-dicarbonyl)dipiperidine (555 mg, 2.2 mM) dissolved in tetrahydrofuran (10 ml) were added. The mixture was then stirred 18 hours, allowing the temperature to rise to ambient, then filtered, and the filter cake washed with tetrahydrofuran. The combined filtrates were evaporated and the residue purified by chromatography on a 10 g reversed phase C18 column, eluting with a gradient from 10 to 50% acetonitrile in water containing 0.1% trifluoroacetic acid. Relevant fractions were combined, evaporated, and the residue rechromatographed on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 20% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the desired product (104 mg). MS (ESP): 474 (MH+) for C22H24FN5O6
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](/[C:11](/[C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=2)=[C:12](/[C:15]2[CH:24]=[CH:23][C:18]3[N:19]([CH3:22])[CH:20]=[N:21][C:17]=3[CH:16]=2)\[CH2:13][CH3:14])=[CH:7][CH:6]=1.[CH3:32][NH2:33]>CO>[CH3:22][N:19]1[C:18]2[CH:23]=[CH:24][C:15](/[C:12](/[CH2:13][CH3:14])=[C:11](\[C:25]3[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=3)/[C:8]3[CH:9]=[CH:10][C:5]([O:4][CH2:3][CH2:2][NH:33][CH3:32])=[CH:6][CH:7]=3)=[CH:16][C:17]=2[N:21]=[CH:20]1
Reactant: CC/C(=C(/c1ccc(O)cc1)c1ccc(OCCCl)cc1)c1ccc2c(c1)ncn2C
Reactant: CN
Solvent: CO
Product: CC/C(=C(/c1ccc(O)cc1)c1ccc(OCCNC)cc1)c1ccc2c(c1)ncn2C

Procedure:
According to the same procedure as example 1, step E described, (E)-4-(1-(4-(2-chloroethoxy)phenyl)-2-(1-methyl-1H-benzo[d]imidazol-5-yl)but-1-enyl)phenol (made by example 8, step F) was reacted with MeNH2 (30% wt in water) in MeOH under reflux to give the desired (E)-product. 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.63 (s, 1H), 7.18 (d, J=8.8 Hz, 2H), 7.13 (d, J=8.4 Hz, 1H), 7.01 (dd, J=8.4 Hz, 1.2 Hz, 1H), 6.88 (d, J=8.8 Hz, 2H), 6.72 (d, J=8.4 Hz, 2H), 6.40 (d, J=8.4 Hz, 2H), 4.10 (t, J=5.2 Hz, 2H), 3.77 (s, 3H), 2.99 (t, J=5.2 Hz, 2H), 2.50-2.55 (m, 5H), 0.91 (t, J=7.2 Hz, 3H); m/z=428[M+1]+.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:23][CH2:24][O:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][O:27]1>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](C(=O)O)c1ccc(O)cc1
Reactant: BrCCOC1CCCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](C(=O)O)c1ccc(OCCOC2CCCCO2)cc1
Temperature: 10 °C
Reaction time: 24 h

Procedure:
(R)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (2.67 g, 10 mmol) (Salituro, G. M.; Townsend, C. A. J. Am. Chem. Soc. 1990, 112, 760-770) was dissolved in N,N-dimethylformamide (70 mL) in an ice bath. Sodium hydride (0.88 g, 60% in mineral oil, 22 mmol) was added in small portions. The mixture was warmed up to 10° C. for 1 hour. 2-(2-Bromo-ethoxy)-tetrahydropyran (1.7 mol, 11 mmol) in N,N-dimethylformamide (20 mL) was added drop wise. The reaction mixture was stirred for 24 hours and then diluted with ice/water. The mixture was extracted with ethyl acetate. The aqueous layer was cooled in an ice bath and acidified using 1.5 M aqueous potassium hydrogen sulfate to pH=2-3. The resulting mixture was extracted with ethyl acetate (5×), washed with water (5×), brine and dried over sodium sulfate. Filtration and evaporation of the solvents gave (R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acid as a solid white foam (3.2 g, 82%).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:39])[NH:7][C:8]([CH:12]([N:18]([C:30](=[O:38])[C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[N:9]2)=[CH:4][CH:3]=1.[CH3:40][C:41]1[CH:42]=[C:43]([CH:46]=[CH:47][CH:48]=1)[CH2:44]Br.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:39])[N:7]([CH2:40][C:41]3[CH:48]=[CH:47][CH:46]=[C:43]([CH3:44])[CH:42]=3)[C:8]([CH:12]([N:18]([C:30](=[O:38])[C:31]3[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=3)[CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:26])[CH3:27])[C:13]([N:15]([CH3:17])[CH3:16])=[O:14])=[N:9]2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(C(=O)N(CCCNC(=O)OC(C)(C)C)C(C(=O)N(C)C)c2nc3cc(Cl)ccc3c(=O)[nH]2)cc1
Reactant: Cc1cccc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(C(=O)N(CCCNC(=O)OC(C)(C)C)C(C(=O)N(C)C)c2nc3cc(Cl)ccc3c(=O)n2Cc2cccc(C)c2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 3-[[1-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-(dimethylamino)-2-oxoethyl](4-methylbenzoyl)amino]propylcarbamate (29 mg, 1 eq.) in dimethyl formamide (1 ml), was added 3-methylbenzyl bromide (8 μl, 1.2 eq.) and potassium carbonate (22 mg, 3 eq.). The reaction mixture was stirred at room temperature overnight. Water was added and the material was extracted into ethyl acetate. Ethyl acetate layer was washed with water, saturated sodium carbonate, saturated sodium chloride, dried over magnesium sulfate, filtered, and evaporated. The product was purified by flash chromatography to give tert-butyl 3-[[1-[7-chloro-3-(3-methylbenzyl)-4-oxo-3,4-dihydroquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl](4-methylbenzoyl)amino]propylcarbamate.
Reaction SMILES: Br.[CH2:2]([N:17]([CH2:19][CH:20]([OH:29])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])C)[CH2:3][N:4]([CH2:6][CH:7]([OH:16])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])C>>[CH2:3]([NH:4][CH2:6][CH:7]([OH:16])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:2][NH:17][CH2:19][CH:20]([OH:29])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCCC(O)CN(C)CCN(C)CC(O)CCCCCCCC
Agent: Br
Product: CCCCCCCCC(O)CNCCNCC(O)CCCCCCCC

Procedure:
In a manner similar to that of Example 22, methylation of N,N'-ethylenebis[2-hydroxydecylamine] (15 g.) and treatment of the resulting product with hydrogen bromide gave N,N'-ethylenebis[N-methyl-2-hydroxydecylamine] (I: R = CH3 (CH2)7, R' = CH3, X = (CH2)2, Z = H) dihydrobromide (4.0 g., m.p. 152.0°-164.0° C.).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[NH:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[C:11]([CH2:16][C:17]1[NH:18][CH:19]=[CH:20][N:21]=1)[CH:10]=2)=[O:6].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C)C=O>[CH3:3][O:4][C:5]([C:7]1[N:8]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[C:11]([CH2:16][C:17]1[NH:21][CH:20]=[CH:19][N:18]=1)[CH:10]=2)=[O:6]
Reactant: COC(=O)c1cc2ccc(Cc3ncc[nH]3)cc2[nH]1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc2ccc(Cc3ncc[nH]3)cc2n1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Sodium hydride (0.17 g. of 50% dispersion in mineral oil) was added portionwise to a stirred solution of 6-(1-imidazolylmethyl)indole-2-carboxylic acid methyl ester (0.90 g.) in dry N,N-dimethylformamide (50 ml.) and the mixture was stirred at room temperature for 1 hour. Benzyl bromide (0.61 g.) was added and the resulting mixture was stirred for 2 hours and then poured into water. The mixture was extracted several times with ethyl acetate and the combined extracts were washed well with water and dried (Na2SO4). Evaporation of the solvent gave an oil which was chromatographed on silica gel. Elution with chloroform first gave mineral oil followed by pure product. Evaporation of the product-containing fractions gave a solid which was crystallized from ethyl acetate/petrol (b.p. 60°-80°) to give 1-benzyl-6-(1-imidazolylmethyl)indole-2-carboxylic acid methyl ester, m.p. 120°-122° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]=1.[CH2:15]([N:17]([CH2:21][CH3:22])[CH2:18][CH2:19][NH2:20])[CH3:16].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([SH:30])=[CH:26][CH:25]=1>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30][C:2]2[CH:7]=[C:6]([NH:20][CH2:19][CH2:18][N:17]([CH2:21][CH3:22])[CH2:15][CH3:16])[N:5]=[C:4]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[N:3]=2)=[CH:26][CH:25]=1
Reactant: CCN(CC)CCN
Reactant: Clc1cc(Cl)nc(-c2ccccc2)n1
Reactant: Sc1ccc(Cl)cc1
Product: CCN(CC)CCNc1cc(Sc2ccc(Cl)cc2)nc(-c2ccccc2)n1

Procedure:
Employing the above procedure, 7.0 g. of 4,6-dichloro-2-phenylpyrimidine is reacted with 34 ml. of N,N-diethylethylenediamine, followed by the reaction of the crude product thereof with 12.5 g. of p-chlorothiophenol. Recrystallization of the crude product (3.85 g.) from n-heptane affords 4-(4-chlorophenylthio)-6-[2-(diethylamino)ethylamino]-2-phenylpyrimidine, m.p. 83.5°-86°C.
Reaction SMILES: [NH2:1][C:2]1([CH2:6][NH:7][C:8]2[C:9]3[S:17][CH:16]=[CH:15][C:10]=3[N:11]=[C:12](Cl)[N:13]=2)[CH2:5][O:4][CH2:3]1.[NH2:18][CH2:19][C:20]1([NH:24][C:25]2[C:26]3[S:34][CH:33]=[CH:32][C:27]=3[N:28]=[C:29](Cl)[N:30]=2)[CH2:23][O:22][CH2:21]1.[CH:35]1[C:40]2[CH2:41][NH:42][CH2:43][CH2:44][S:45](=[O:47])(=[O:46])[C:39]=2[CH:38]=[CH:37][CH:36]=1>C(O)CCC>[NH2:1][C:2]1([CH2:6][NH:7][C:8]2[C:9]3[S:17][CH:16]=[CH:15][C:10]=3[N:11]=[C:12]([N:42]3[CH2:41][C:40]4[CH:35]=[CH:36][CH:37]=[CH:38][C:39]=4[S:45](=[O:47])(=[O:46])[CH2:44][CH2:43]3)[N:13]=2)[CH2:5][O:4][CH2:3]1.[NH2:18][CH2:19][C:20]1([NH:24][C:25]2[C:26]3[S:34][CH:33]=[CH:32][C:27]=3[N:28]=[C:29]([N:42]3[CH2:41][C:40]4[CH:35]=[CH:36][CH:37]=[CH:38][C:39]=4[S:45](=[O:47])(=[O:46])[CH2:44][CH2:43]3)[N:30]=2)[CH2:23][O:22][CH2:21]1
Reactant: NC1(CNc2nc(Cl)nc3ccsc23)COC1
Reactant: NCC1(Nc2nc(Cl)nc3ccsc23)COC1
Reactant: O=S1(=O)CCNCc2ccccc21
Solvent: CCCCO
Product: NC1(CNc2nc(N3CCS(=O)(=O)c4ccccc4C3)nc3ccsc23)COC1
Product: NCC1(Nc2nc(N3CCS(=O)(=O)c4ccccc4C3)nc3ccsc23)COC1
Temperature: 160 °C

Procedure:
A mixture of N-[(3-aminooxetan-3-yl)methyl]-2-chlorothieno[3,2-d]pyrimidin-4-amine and N-[3-(aminomethyl)oxetan-3-yl]-2-chlorothieno[3,2-d]pyrimidin-4-amine (184 mg, 0.66 mmol), 6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptene-5,5-dioxide (680 mg, 3.44 mmol) in n-Butanol (1 mL) was heated at 160° C. for 30 min. The crude was purified by preparative HPLC to afford N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine and N-[3-(aminomethyl)oxetan-3-yl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)thieno[3,2-d]pyrimidin-4-amine.
Reaction SMILES: [C:1]1([C:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:9][CH2:10][OH:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.Cl>N1C=CC=CC=1>[S:30]([O:11][CH2:10][CH2:9][C:8]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([C:27]1[CH:28]=[CH:29][C:24]([CH3:34])=[CH:25][CH:26]=1)(=[O:32])=[O:31]
Reactant: OCCC(=C(c1ccccc1)c1ccccc1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCC(=C(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Temperature: 0 °C

Procedure:
The reaction is performed under dry conditions. 30.0 g of 1,1,2-triphenyl-1-butene-4-ol are dissolved in 100 ml of dry pyridine. Then with stirring and cooling the mixture on ice, 57.0 g of 4-toluenesulfonic acid chloride in 50 ml of dry pyridine are added dropwise to the mixture. The mixture is stirred for 6 h at 0° C. Then 250 ml of ice-cold water and 750 ml of cold 2M hydrochloric acid are added. The precipitate is collected by filtration and washed with water. Finally the product is recrystallized from ethanol. The yield is 36.8 g (81%) of a product having m.p. 137°-9° C.