Cesium carbonate → tert-Butyl-6-(((1S,2S)-2-(5-(2-hydroxypropan-2-yl)pyridin-2-yl)cyclopropyl)methoxy)-2-methylpyrimidin-4-yl((5-methyl-1,3,4-thiadiazol-2-yl)methyl)carbamate

HRID 2175417Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:13][C@@H:12]2[C:14]2[N:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[CH3:24][C:25]1[S:29][C:28]([CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[N:27][N:26]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:34]([O:33][C:32](=[O:38])[N:31]([C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:13][C@@H:12]2[C:14]2[CH:15]=[CH:16][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:18][N:19]=2)[N:5]=[C:6]([CH3:8])[N:7]=1)[CH2:30][C:28]1[S:29][C:25]([CH3:24])=[N:26][N:27]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

Conditions

Temperature: 85 °C

Procedure

The mixture of 8-3 (60 mg, 0.18 mmol), 8-4 (50 mg, 0.22 mmol), Cs2CO3 (88 mg, 0.27 mmol), Pd(OAc)2 (8.1 mg, 0.036 mmol), BINAP (25 mg, 0.040 mmol) in toluene (2.0 mL) was heated at 85° C. for overnight. Then the reaction mixture was diluted with EtOAc (20 mL), filtered and concentrated in vacuo to give crude product (94 mg) which was used for next step without further purification. LRMS (ES) calculated M+H for C26H34N6O4S: 527.24. Found: 527.2.

Workup

filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-129b659238bb44ecbe90d2caf4204167
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062059B2

Reaction notes

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