Cesium carbonate → HCID 178462219, compound

HRID 712015Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]#[C:9][C@H:10]([OH:12])[CH3:11])=[CH:6][N:5]=[C:4]2[CH:13]=[CH:14][S:15][C:3]=12.Cl.[NH2:17][C@H:18]1[CH2:23][CH2:22][C@H:21]([CH2:24][C:25]#[N:26])[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:12][C@@H:10]([C:9]1[N:17]([C@H:18]2[CH2:23][CH2:22][C@H:21]([CH2:24][C:25]#[N:26])[CH2:20][CH2:19]2)[C:2]2=[C:3]3[S:15][CH:14]=[CH:13][C:4]3=[N:5][CH:6]=[C:7]2[CH:8]=1)[CH3:11]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (2R)-4-(7-chlorothieno[3,2-b]pyridin-6-yl)but-3-yn-2-ol (0.055 g, 0.23 mmol), (trans-4-aminocyclohexyl)acetonitrile hydrochloride (0.040 g, 0.23 mmol), cesium carbonate (0.19 g, 0.58 mmol), palladium acetate (5.2 mg, 0.023 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (27 mg, 0.046 mmol) in toluene (1.1 mL) was purged with N2 for 3 times. The resulting mixture was stirred at 100° C. for 2 h, then at 120° C. for 2 h. The mixture was filtered. The filtrate was concentrated under reduced pressure, diluted with MeOH and purified on prep-LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (1.4 mg, 1.8%). LCMS calculated for C19H22N3OS (M+H)+: m/z=340.1. Found: 340.1.

Workup

customwas purged with N2 for 3 times
waitat 120° C. for 2 h
filtrationThe mixture was filtered
concentrationThe filtrate was concentrated under reduced pressure
additiondiluted with MeOH
custompurified on prep-LCMS (XBridge C18 column
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record: ord-dfa468b98b0543e1b144ebd37a010152
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181271B2

Reaction notes

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