Dichloromethane → [3-(4-Amino-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-benzyl]-carbamic acid tert-butyl ester

HRID 1972757Notes

Reaction equation

[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:26]1[N:34]2[C:29]([C:30]([NH2:35])=[N:31][CH:32]=[N:33]2)=[CH:28][CH:27]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6](=[O:24])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:26]2[N:34]3[C:29]([C:30]([NH2:35])=[N:31][CH:32]=[N:33]3)=[CH:28][CH:27]=2)[CH:10]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of [3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-carbamic acid tert-butyl ester (7 g, 21 mmol) in DME (100 mL), 7-bromo-pyrrolo[2,1-f][1,2,4]triazin-4-ylamine (2.5 g, 11.7 mmol), PdCl2(dppf) complexed with CH2Cl2 (850 mg, 1.2 mmol) and 2 N Na2CO3 (12 mL) were added. The mixture was degassed for 20 min and was then heated to 80° C. for 23 hours. After cooling, the mixture was partitioned between EtOAc and H2O, and the organic layer was separated and dried. Biotage® chromatography (50-100% EtOAc) provided the title product as off white solid 2.6 g (76%). 1H NMR (300 MHz, DMSO-d6) δ 7.80-7.50 (m, 6 H), 7.20-7.0 (m, 3 H), 4.80 (s, 2 H), 1.30 (s, 9 H); ES-MS m/z 339 [M+H]+, HPLC RT (min) 2.41.

Workup

additionwere added
customThe mixture was degassed for 20 min
temperatureAfter cooling
customthe mixture was partitioned between EtOAc and H2O
customthe organic layer was separated
customdried

Sources & evidence

ORD record: ord-8e80b09cc79f4c848ef407b99b1d7fc0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431695B2

Reaction notes

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