Sodium hydride → (1S,4R)-4-[3-(cis-2,6-Dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 630864Notes

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.[CH3:15][C@H:16]1[CH2:21][CH2:20][CH2:19][C@@H:18]([CH3:22])[N:17]1[C:23]1[N:27]2[CH:28]=[C:29](F)[CH:30]=[CH:31][C:26]2=[N:25][N:24]=1>CN(C=O)C>[CH3:15][C@H:16]1[CH2:21][CH2:20][CH2:19][C@@H:18]([CH3:22])[N:17]1[C:23]1[N:27]2[CH:28]=[C:29]([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:30]=[CH:31][C:26]2=[N:25][N:24]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of sodium hydride (60% in mineral oil, 323 mg, 8.06 mmol) in DMF (10.0 mL) was added (1R,4S)-4-amino-1,2,3,4-tetrahydro-naphthalen-1-ol (329 mg, 2.02 mmol) and the reaction stirred for 20 min. Intermediate 96b (500 mg, 2.02 mmol) was added in DMF (2.00 mL) and the reaction heated to 60° C. for 1 h. The reaction was cooled and quenched by dropwise addition of methanol, before being diluted with methanol and loaded onto an SCX-2 cartridge, which was washed with MeOH. The product was eluted with 2M NH3 in MeOH. The residue was purified by FCC, using 0-10% (2M NH3 in MeOH) in DCM, to give the title compound (453 mg, 57%). LCMS (Method 4): Rt 2.13, m/z 392 [MH+].

Workup

temperatureThe reaction was cooled
customquenched by dropwise addition of methanol
additionbefore being diluted with methanol
washwas washed with MeOH
washThe product was eluted with 2M NH3 in MeOH
customThe residue was purified by FCC

Sources & evidence

ORD record: ord-73f0b73c9bd44d16a21d642ac43aa903
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315503B2

Reaction notes

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