Water → HCID 66612153, compound

HRID 1621999Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]([C:16]2[CH:17]=[C:18](B(O)O)[C:19]([F:22])=[N:20][CH:21]=2)[CH3:15])[C@H:10]([CH3:26])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:28]1[N:33]=[C:32]([CH3:34])[N:31]=[C:30]([N:35]([CH2:45][C:46]2[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=2)[CH2:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)[N:29]=1.O1CCOCC1.C([O-])(=O)C.[K+].O.CC(N)CC1C=CC=CC=1.OP(O)(O)=O>>[CH3:53][O:52][C:49]1[CH:48]=[CH:47][C:46]([CH2:45][N:35]([CH2:36][C:37]2[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[C:30]2[N:31]=[C:32]([CH3:34])[N:33]=[C:28]([C:18]3[CH:17]=[C:16]([CH:14]([N:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C@H:10]4[CH3:26])[CH3:15])[CH:21]=[N:20][C:19]=3[F:22])[N:29]=2)=[CH:51][CH:50]=1

Participants

Reactant 6

HCID 962Water

HCID 312751,4-Dioxane

HCID 62885Benzeneethanamine, alpha-methyl-, phosphate (1:1)

HCID 517044Potassium Acetate

HCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HCID 68512791HCID 68512791, compound

Product 1

HCID 66612153HCID 66612153, compound

Conditions

Temperature: 120 °C

Procedure

A glass microwave reaction vessel was charged with 5-(1-((R)-4-(tert-butoxycarbonyl)-2-methylpiperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (1.4 g, 3.81 mmol),4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.467 g, 3.81 mmol),1,4-dioxane (10 mL, 3.81 mmol), potassium acetate (1.122 g, 11.44 mmol), water (1 mL, 3.81 mmol), and amphos (0.270 g, 0.381 mmol). The reaction mixture was stirred and heated in a microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 120° C. for 20 min (watts, Powermax feature, ramp time min). LC/MS showed desired product, starting triazine and debornated product. The reaction mixture was diluted with water (20 mL) and DCM (25 mL) and the aqueous layer was extracted with DCM (3×50 mL) dried over sodium sulfate, filtered and concentrated in vacuum. The crude product was adsorbed onto a plug of silica gel and chromatographed through a silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide (3R)-tert-butyl 4-(1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (1.26 g, 1.876 mmol, 49.2% yield).

Workup

customA glass microwave reaction vessel

Sources & evidence

ORD record: ord-85ef5276da7f45959baed22ef1b43b1c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772480B2

Reaction notes

Loading…