Ammonia → (1S,4R)-4-[3-(1-Dimethylamino-1-methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 630809Notes

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]([N:28]([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[N:23][N:24]=2)[CH:21]=1.N>CN(C=O)C.CO.C(Cl)Cl>[CH3:30][N:28]([CH3:29])[C:25]([C:22]1[N:20]2[CH:21]=[C:16]([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:17]=[CH:18][C:19]2=[N:24][N:23]=1)([CH3:27])[CH3:26]

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of NaH (60% in mineral oil, 112 mg, 2.80 mmol) in DMF (2.50 mL) was added Intermediate A (114 mg, 0.70 mmol) and the reaction stirred for 20 min. Intermediate 76b (153 mg, 0.70 mmol) was added in DMF (2.50 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; concentration in vacuo gave a residue. FCC, using 2-10% [2M NH3 in MeOH] in DCM, gave the title compound (120 mg, 47%). LCMS (Method 4): Rt 0.31, m/z 366 [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
concentrationconcentration in vacuo
customgave a residue

Sources & evidence

ORD record: ord-8a1e37bbd8a24b84b7913be8f5af9054
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315503B2

Reaction notes

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