Sodium hydride → HCID 117729017, compound

HRID 2200031Notes

Reaction equation

[H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.[Cl:15][C:16]1[CH:21]=[C:20]([CH2:22][N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)[CH:19]=[C:18]([Cl:30])[C:17]=1[C:31]1[N:35]2[CH:36]=[C:37](F)[CH:38]=[CH:39][C:34]2=[N:33][N:32]=1>CN(C=O)C>[Cl:15][C:16]1[CH:21]=[C:20]([CH2:22][N:23]2[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]2)[CH:19]=[C:18]([Cl:30])[C:17]=1[C:31]1[N:35]2[CH:36]=[C:37]([O:14][C@H:7]3[C:8]4[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=4)[C@@H:4]([NH2:3])[CH2:5][CH2:6]3)[CH:38]=[CH:39][C:34]2=[N:33][N:32]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of sodium hydride (60% dispersion in oil, 56 mg, 1.39 mmol) in dry DMF (2.0 mL) under nitrogen was treated with Intermediate 1 (46 mg, 0.28 mmol) and the mixture was stirred for 20 min. Intermediate 13d (110 mg, 0.28 mmol) was added and the mixture was heated to 60° C. for 1.75 h then quenched with MeOH. The mixture was further diluted with MeOH and applied to a pre-conditioned (MeOH) SCX-2 cartridge (10g). The cartridge was eluted with MeOH then 2M NH3 in MeOH. The relevant fractions were combined and concentrated in vacuo. The residue was dissolved in DCM containing a few drops of MeOH and purified by FCC, using 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (28 mg, 19%). LCMS (Method 3): Rt 2.08 min, m/z 537, 539 [MH+].

Workup

customthen quenched with MeOH
additionThe mixture was further diluted with MeOH
washThe cartridge was eluted with MeOH
concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in DCM containing a few drops of MeOH
custompurified by FCC

Sources & evidence

ORD record: ord-86fe9426aef54eccb0785303799f0a8c
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359354B2

Reaction notes

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