Dimethylacetamide → HCID 118036555, compound

HRID 1777920Notes

Reaction equation

Br[C:2]1[C:3]([O:9][C@H:10]2[CH2:14][CH2:13][O:12][CH2:11]2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.C[C:16]([N:18](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.[Fe+2]>[NH2:8][C:5]1[N:4]=[C:3]([O:9][C@H:10]2[CH2:14][CH2:13][O:12][CH2:11]2)[C:2]([C:16]#[N:18])=[CH:7][N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

(S)-5-bromo-4-((tetrahydrofuran-3-yl)oxy)pyrimidin-2-amine (intermediate 64, 38 mg, 0.146 mmol), zinc cyanide (18.0 mg, 0.153 mmol), zinc (1.9 mg, 0.029 mmol), Pd2(dba)3 (13.4 mg, 0.015 mmol) and dppf (16.2 mg, 0.029 mmol) were treated with DMA (2 ml) under argon and stirred at 100° C. for 16 h. The reaction mixture was cooled to room temperature, quenched with sat. aq. NaHCO3 and diluted with EtOAc. The organic layer was separated, washed with water (2×) and brine (2×), dried over Na2SO4, filtered and concentrated. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) to give the title compound as a brown solid. (UPLC-MS 3) tR 0.54 min; ESI-MS 207.2 [M+H]+.

Workup

temperatureThe reaction mixture was cooled to room temperature
customquenched with sat. aq. NaHCO3
additiondiluted with EtOAc
customThe organic layer was separated
washwashed with water (2×) and brine (2×)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)

Sources & evidence

ORD record: ord-8304baf4df254fa4a290794fb65411f5
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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