1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → N-(5-bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-4-(morpholinomethyl)thiazol-2-amine

HRID 1684954

Reaction equation

[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5](Br)=[N:4][CH:3]=1.[O:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[N:20]=[C:21]([NH2:24])[S:22][CH:23]=2)[CH2:14][CH2:13]1.CC(C)([O-])C.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd]>[Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:24][C:21]2[S:22][CH:23]=[C:19]([CH2:18][N:15]3[CH2:16][CH2:17][O:12][CH2:13][CH2:14]3)[N:20]=2)=[N:4][CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Intermediate 3 (5,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine, 140 mg, 0.50 mmol), Intermediate 6 (4-(1-morpholinomethyl) thiazol-2-ylamine, 120 mg, 0.60 mmol), sodium tert-butoxide (68 mg, 0.71 mmol), palladium dibenzylidene acetone (19 mg, 0.02 mmol) and Xantphos (23 mg, 0.04 mmol) were suspended in toluene (4 mL). The mixture is degassed with nitrogen for 5 min and then stirred at 90° C. for 16 h. The solvent is evaporated in vacuo to leave a brown residue. The residue is purified by column chromatography, eluting with 2% methanolic ammonia (7 N) in dichloromethane to give the title compound as a yellow powder (53 mg, 27%). 1H NMR (400 MHz, d6-DMSO) δ 2.53 (s, 4H, CH2CH2), 3.51 (s, 2H, CH2), 3.61 (m, 4H, CH2CH2), 6.99 (s, 1H), 8.13 (s, 1H), 8.61 (s, 1H), 8.75 (s, 1H).

Workup

customThe mixture is degassed with nitrogen for 5 min
customThe solvent is evaporated in vacuo
customto leave a brown residue
customThe residue is purified by column chromatography
washeluting with 2% methanolic ammonia (7 N) in dichloromethane

Sources & evidence

ORD record: ord-f85e440e0c1a4d139be12b587a351691
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148369B2

Linked notes

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