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

HRID 572113Notes

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+].[CH:15]1([C:21]2[N:25]3[CH:26]=[C:27](F)[CH:28]=[CH:29][C:24]3=[N:23][N:22]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>CN(C=O)C>[CH:15]1([C:21]2[N:25]3[CH:26]=[C:27]([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:28]=[CH:29][C:24]3=[N:23][N:22]=2)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

Conditions

Temperature: 60 °C

Procedure

An opaque brown solution of Intermediate 1d (171 mg, 1.05 mmol) and sodium hydride (60% dispersion in oil, 120 mg, 3.00 mmol) in dry DMF (2 mL) was stirred at RT under Argon for 30 min. Intermediate 34b (219 mg, 1.00 mmol) was added, and the resulting dark solution stirred at 60° C. for 2 h. The cooled solution was concentrated in vacuo, redissolved in MeOH (2 mL), applied to an SCX-2 cartridge, and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo left a brown oil. Flash chromatography (silica 25 g, 2-10% [2M NH3 in MeOH] in DCM) gave a yellow oil. Freeze-drying from MeCN-water (1:2, 3 mL) left the title compound as a pale yellow solid (203 mg, 56%). LCMS (Method 3): Rt 2.29 min, m/z 363 [MH+].

Workup

concentrationThe cooled solution was concentrated in vacuo
dissolutionredissolved in MeOH (2 mL)
washwashed with MeOH
washThe product was eluted with 2M NH3 in MeOH
concentrationconcentration in vacuo
waitleft a brown oil
customFlash chromatography (silica 25 g, 2-10% [2M NH3 in MeOH] in DCM) gave a yellow oil
dry with materialFreeze-drying from MeCN-water (1:2, 3 mL)
waitleft the title compound as a pale yellow solid (203 mg, 56%)

Sources & evidence

ORD record: ord-c21443b5565849dfa36629c7583e1f46
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029373B2

Reaction notes

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