Sodium hydride → (1S,3S)-3-[3-((S)-1-Methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1-ylamine

HRID 1402153Notes

Reaction equation

[NH2:1][C@@H:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C@@H:4]([OH:11])[CH2:3]1.[H-].[Na+].F[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C@@H:24]3[CH2:28][CH2:27][CH2:26][N:25]3[CH3:29])=[N:22][N:23]=2)[CH:20]=1>CN(C=O)C.O>[CH3:29][N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:21]1[N:19]2[CH:20]=[C:15]([O:11][C@@H:4]3[C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[C@@H:2]([NH2:1])[CH2:3]3)[CH:16]=[CH:17][C:18]2=[N:23][N:22]=1

Participants

Conditions

Temperature: 60 °C

Procedure

(1S,3S)-3-Amino-indan-1-ol (110 mg, 0.74 mmol) was added to a suspension of NaH (60% in mineral oil, 87 mg, 2.17 mmol) in anhydrous DMF (5 mL) at RT and stirred for 20 min. Intermediate 5b (160 mg, 0.72 mmol) was then added in one portion and the mixture heated at 60° C. for 3 h. After cooling the mixture was diluted with water (20 mL) and extracted with EtOAc (3×50 mL). The combined organics were washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by FCC, using 0-10% MeOH in DCM, to give the title compound as give a foam (132 mg, 52%). LCMS (Method 1): Rt 0.34 min, m/z 350 [MH+]. 1H NMR (300 MHz, CDCl3): 1.95-2.16 (6H, m), 2.24 (3H, s), 2.26-2.45 (2H, m), 2.77 (1H, ddd, J 14.1, 7.0, 2.0), 3.23-3.30 (1H, m), 4.02-4.09 (1H, m), 4.71 (1H, t, J 6.8), 5.68 (1H, dd, J 6.2, 1.9), 7.04 (1H, dd, J 9.9, 2.2), 7.29-7.50 (4H, m), 7.64 (1H, dd, J 9.9, 0.9), 8.35 (1H, d, J 2.2).

Workup

temperatureAfter cooling the mixture
extractionextracted with EtOAc (3×50 mL)
washThe combined organics were washed with brine (50 mL)
dry with materialdried (MgSO4)
customevaporated in vacuo
customThe residue was purified by FCC

Sources & evidence

ORD record: ord-dfa33627bc3b4b2f8b462f8682c460dc
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08907094B2

Reaction notes

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