Sodium hydride → (1S,4R)-4-[3-(1-Dimethylamino-cyclopentyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 2285153Notes

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.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([C:25]3([N:30]([CH3:32])[CH3:31])[CH2:29][CH2:28][CH2:27][CH2:26]3)=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[CH3:31][N:30]([CH3:32])[C:25]1([C:22]2[N:20]3[CH:21]=[C:16]([O:14][C@H:7]4[C:8]5[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=5)[C@@H:4]([NH2:3])[CH2:5][CH2:6]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

To a suspension of sodium hydride (60% in mineral oil, 133 mg, 3.34 mmol) in DMF (5 mL) was added Intermediate A (136 mg, 0.83 mmol) and the reaction mixture was stirred for 20 min. A solution of Intermediate 99c (207 mg, 0.83 mmol) in DMF (3 mL) was added and the reaction mixture was heated at 60° C. for 90 min. After cooling, the reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% (2M NH3 in MeOH) in DCM, to give the title compound (211 mg, 65%). LCMS (Method 4): Rt 1.49 min, m/z 392 [MH+].

Workup

temperatureAfter cooling
customthe reaction mixture was quenched by careful addition of MeOH
washThe cartridge was washed with MeOH
washthe product eluted with 2M NH3 in MeOH
additionThe product containing fractions
concentrationwere concentrated in vacuo
customthe resultant residue was purified by FCC on silica

Sources & evidence

ORD record: ord-12436597333a47f88bc3e16050e2d9a1
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09145413B2

Reaction notes

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