Diisopropylethylamine → HCID 117738603, compound

HRID 1506996Notes

Reaction equation

HRID 1506996 reaction equation
[F-].[K+].[NH2:3][C@H:4]([C:6]1[N:15]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[C:14](=[O:22])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[Cl:23])[N:7]=1)[CH3:5].[NH2:24][C:25]1[N:30]=[C:29]([NH2:31])[C:28]([C:32]#[N:33])=[C:27](Cl)[N:26]=1.[CH:35](N(C(C)C)CC)(C)C>CS(C)=O>[NH2:24][C:25]1[N:30]=[C:29]([NH2:31])[C:28]([C:32]#[N:33])=[C:27]([NH:3][C@H:4]([C:6]2[N:15]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)[C:14](=[O:22])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[Cl:23])[N:7]=2)[CH2:5][CH3:35])[N:26]=1.[NH2:24][C:25]1[N:30]=[C:29]([NH2:31])[C:28]([C:32]#[N:33])=[C:27]([NH:3][C@H:4]([C:6]2[N:15]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)[C:14](=[O:22])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[Cl:23])[N:7]=2)[CH3:5])[N:26]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrileHCID 90232554HCID 90232554, compound

Product 2

HCID 86763164HCID 86763164, compoundHCID 117738603HCID 117738603, compoundYield 166%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Potassium fluoride (138 mg, 2.38 mmol) was added to a solution of (S)-2-(1-aminoethyl)-5-chloro-3-(pyridin-3-yl)quinazolin-4(3H)-one (400 mg, 1.33 mmol) and 2,4-diamino-6-chloropyrimidine-5-carbonitrile (237 mg, 1.4 mmol) in diisopropylethylamine (1.0 mL, 6.0 mmol) and DMSO (3 mL). The resultant mixture was heated to 90° C. for 14 hours. Then it was cooled to room temperature, filtered, and purified by HPLC eluting with 5%-95% water/acetonitrile (0.1% v/v trifluoroacetic acid). The appropriate fractions were pooled and lyophilized to obtain the title compound of (S)-2,4-diamino-6-((1-(5-chloro-4-oxo-3-(pyridin-3-yl)-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile as a solid (479 mg). 1H NMR (400 MHz, DMSO) δ 8.74 (d, J=2.4 Hz, 0.5H), 8.58 (dd, J=4.8, 1.5 Hz, 0.5H), 8.51 (dd, J=4.9, 1.7 Hz, 1.5H), 8.06 (dm, J=8.5 Hz, 0.5H), 7.85 (dm, J=8.0 Hz, 0.5H), 7.8 (td, J=8.1, 1.4 Hz, 1H), 7.68 (ddd, J=8.2, 3.9, 1.2 Hz, 1H), 7.60 (dt, J=7.9, 1.3 Hz, 1H), 7.55 (ddd, J=8.1, 4.8, 0.7 Hz, 0.5H), 7.48 (ddt, J=8.1, 4.8, 0.7 Hz, 0.5H), 4.85 (m, 1H), 1.35 (d, J=6.8 Hz, 3H). ES/MS 434.1 (M+H+).

Workup

  1. filtrationfiltered
  2. custompurified by HPLC
  3. washeluting with 5%-95% water/acetonitrile (0.1% v/v trifluoroacetic acid)

Sources & evidence

ORD record
ord-72845a0d7e394ee89e3222a627a5a623
Source dataset
uspto-grants-2015_12
Patent number
US09221795B2

Reaction notes

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