Sodium hydride → HCID 86687091, compound

HRID 2282520Notes

Reaction equation

[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]3[CH2:29][CH2:28][CH2:27][CH2:26]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[N:25]1([C:22]2[N:20]3[CH:21]=[C:16]([O:12][C@H:5]4[C:6]5[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=5)[C@@H:2]([NH2:1])[CH2:3][CH2:4]4)[CH:17]=[CH:18][C:19]3=[N:24][N:23]=2)[CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

Conditions

Temperature: 60 °C

Procedure

Intermediate A (222 mg, 1.36 mmol) was added to a mixture of NaH (60% in mineral oil, 163 mg, 4.08 mmol) in DMF (15 mL) at RT and stirred for 30 min. Intermediate 75a (280 mg, 1.36 mmol) was then added and the resulting mixture heated to 60° C. for 1 h. After cooling, the reaction was quenched with sat. aq. NH4Cl solution. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were washed with sat. aq. NaHCO3 solution and brine, and concentrated in vacuo. The resulting residue was purified by FCC, using 0 to 15% [2M NH3 in MeOH] in DCM, to afford the title compound as a brown solid (65.0 mg, 14%). LCMS (Method 3): Rt 1.89 min, m/z 350 [MH+].

Workup

temperatureAfter cooling
customthe reaction was quenched with sat. aq. NH4Cl solution
additionThe mixture was diluted with water
extractionextracted with EtOAc
washThe combined organic extracts were washed with sat. aq. NaHCO3 solution and brine
concentrationconcentrated in vacuo
customThe resulting residue was purified by FCC

Sources & evidence

ORD record: ord-82b6b4b2718e46e8a228431919fc7f68
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139584B2

Reaction notes

Loading…