Ammonia → (1S,4R)-4-[3-((S)-1,2-Dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-ylamine

HRID 1402174Notes

Reaction equation

[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@:3]1([C:8]1[N:12]2[CH:13]=[C:14](F)[CH:15]=[CH:16][C:11]2=[N:10][N:9]=1)[CH3:7].[NH2:18][C@@H:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:22]([OH:29])[CH2:21][CH2:20]1.[H-].[Na+].N>CN(C=O)C.CO.C(Cl)Cl>[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@:3]1([C:8]1[N:12]2[CH:13]=[C:14]([O:29][C@H:22]3[C:23]4[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=4)[C@@H:19]([NH2:18])[CH2:20][CH2:21]3)[CH:15]=[CH:16][C:11]2=[N:10][N:9]=1)[CH3:7]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of Intermediate 47b (150 mg, 0.64 mmol) and Intermediate A (126 mg, 0.64 mmol) in DMF (3 mL) was added NaH (60% in mineral oil, 90 mg, 2.24 mmol) portionwise. The mixture was stirred at 60° C. for 1.5 h then allowed to cool to RT. The mixture was carefully quenched by pouring into MeOH (10 mL), then applied to an SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3 in MeOH; concentration in vacuo gave a residue. FCC, using 0-10% [2M NH3 in MeOH] in DCM, gave the title compound as a brown solid (180 mg, 75%). LCMS (Method 4): Rt 0.49, m/z 378 [MH+].

Workup

temperatureto cool to RT
customThe mixture was carefully quenched
additionby pouring into MeOH (10 mL)
washwashed with MeOH
washThe product was eluted with 2M NH3 in MeOH
concentrationconcentration in vacuo
customgave a residue

Sources & evidence

ORD record: ord-67a3a4a56f9f4418b5e84d5830cae885
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08907094B2

Reaction notes

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