Cesium carbonate → (5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone

HRID 1923346Notes

Reaction equation

HRID 1923346 reaction equation
Cl[C:2]1[N:3]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:5]2[N:10]=[C:9]([C:11]([N:13]3[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]3)=[O:12])[S:8][C:6]=2[N:7]=1.[CH2:29]([C:31]1[NH:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1)[CH3:30].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:29]([C:31]1[N:32]([C:2]2[N:3]=[C:4]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[C:5]3[N:10]=[C:9]([C:11]([N:13]4[CH2:14][CH2:15][CH:16]([C:19]([OH:22])([CH3:20])[CH3:21])[CH2:17][CH2:18]4)=[O:12])[S:8][C:6]=3[N:7]=2)[C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1)[CH3:30]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605242(5-Chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-[4-(1-hydroxy-1-methylethyl)piperidin-1-yl]methanone

Product 1

HCID 49833479(5-(2-ethyl-1H-benzo[d]imidazol-1-yl)-7-morpholinothiazolo[5,4-d]pyrimidin-2-yl)(4-(2-hydroxypropan-2-yl)piperidin-1-yl)methanone

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (5-chloro-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-yl)-[4-(1-hydroxy-1-methylethyl)piperidin-1-yl]methanone (250 mg, 0.59 mmol), 2-ethylbenzimidazole (90 mg, 0.62 mmol), tris(dibenzylideneacetone)dipalladium (15 mg, 2.5 mol %), XPhos (25 mg, 10 mol %) and Cs2CO3 (270 mg, 0.83 mmol) in DMF (6 mL) was purged with argon then heated at 150° C. for 30 min in a microwave reactor. The reaction mixture was purified by column chromatography (Si-PCC, MeOH:DCM, 1-5%) followed by recrystallisation from Et2O and EtOAc affording 771 (109 mg, 35%). LCMS (method I): RT 3.96 min [M+H]+ 536.3. 1H NMR (CDCl3, 400 MHz): δ 8.06-8.05 (1 H, m), 7.76-7.75 (1 H, m), 7.32-7.28 (2 H, m), 5.22 (1 H, d, J=13.34 Hz), 4.84 (1 H, d, J=13.16 Hz), 4.41 (4 H, brd s), 3.89 (4 H, t, J=4.74 Hz), 3.37 (2 H, q, J=7.46 Hz), 3.17-3.15 (1 H, m), 2.84-2.82 (1 H, m), 1.94 (2 H, t, J=13.72 Hz), 1.72-1.62 (1 H, m), 1.49-1.40 (5 H, m), 1.23 (6 H, d, J=7.01 Hz)

Workup

  1. customwas purged with argon
  2. customThe reaction mixture was purified by column chromatography (Si-PCC, MeOH:DCM, 1-5%)
  3. customfollowed by recrystallisation from Et2O and EtOAc affording 771 (109 mg, 35%)
  4. customRT 3.96 min [M+H]+ 536.3

Sources & evidence

ORD record
ord-977bee760c09456d8bb3c44c24dfe6f9
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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