Triphenylphosphine → 7-[(1R)-1-(6-chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethoxy]furo[3,2-c]pyridin-6-amine

HRID 912059Notes

Reaction equation

[N+:1]([C:4]1[N:9]=[CH:8][C:7]2[CH:10]=[CH:11][O:12][C:6]=2[C:5]=1[OH:13])([O-])=O.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C@@H:24](O)[CH3:25])=[N:22][N:23]=2)[N:20]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>Cl.[Fe].CCO.C1COCC1>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C@H:24]([O:13][C:5]3[C:6]4[O:12][CH:11]=[CH:10][C:7]=4[CH:8]=[N:9][C:4]=3[NH2:1])[CH3:25])=[N:22][N:23]=2)[N:20]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a mixture of 6-nitrofuro[3,2-c]pyridin-7-ol (50.0 mg, 0.278 mmol), (S)-1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-ethanol (110 mg, 0.555 mmol), triphenylphosphine (191 mg, 1.11 mmol) and THF (10 mL) under nitrogen at rt was added diisopropyl azodicarboxylate (0.219 mL, 1.11 mmol) dropwise. The solution was heated to 40° C. for 2 h. The solvent was removed in vacuo, and EtOH (20 mL), iron powder (200 mg, 3 mmol) and conc. HCl (8 drops) were added. The mixture was heated to 75° C. for 1 h. The material was loaded into a SCX cartridge, washed with MeOH and ejected with 2M NH3 in MeOH. The filtrate was concentrated in vacuo to afford the title compound as a dark orange solid, and was used in the next step without further purification. MS (ES+): m/z 331.02 (100) [MH+]. HPLC: tR=1.92 min (ZQ3, polar—5 min).

Workup

additionwere added
temperatureThe mixture was heated to 75° C. for 1 h
washwashed with MeOH
concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record: ord-89ed1ea2c32e4c8794f1f88e9d30ad02
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022206B2

Reaction notes

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