Diisopropylethylamine → 2,2-dimethylpropionic acid 2-[(R)-3-(5-fluoro-2-{(S)-2-[9-(tetrahydropyran-2-yl)-9H-purin-6-ylamino]butyrylamino}phenylamino)piperidin-1-yl]ethyl ester

HRID 243030Notes

Reaction equation

[NH2:1][C@@H:2]([CH2:29][CH3:30])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[NH:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][CH2:21][O:22][C:23](=[O:28])[C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:15]1)=[O:4].Cl[C:32]1[N:40]=[CH:39][N:38]=[C:37]2[C:33]=1[N:34]=[CH:35][N:36]2[CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][O:42]1.CCN(C(C)C)C(C)C>C(O)CCC>[F:12][C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:32]2[N:40]=[CH:39][N:38]=[C:37]3[C:33]=2[N:34]=[CH:35][N:36]3[CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)[CH2:29][CH3:30])=[C:7]([NH:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][CH2:21][O:22][C:23](=[O:28])[C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:15]2)[CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2,2-dimethylpropionic acid 2-{(R)-3-[2-((S)-2-aminobutyrylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester (0.588 g, 1.39 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.333 g, 1.39 mmol), and DIPEA (0.71 mL, 4.15 mmol) in n-butanol (6 mL) was stirred in a sealed vial at 100° C. for 16 h. After cooling to RT, volatiles were removed in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM) affording the title compound as a light brown gum (0.516 g, 59%). LCMS (Method B): RT 2.47 min [M+H]+ 625.

Workup

temperatureAfter cooling to RT
customvolatiles were removed in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 2-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record: ord-8306779419ee48139a9380f85e4bffec
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

Loading…