1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 67111760, compound

HRID 1177562Notes

Reaction equation

HRID 1177562 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[C:12]([C:17]2([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[CH2:19][CH2:18]2)[N:11]=3)=[C:4]([F:26])[CH:3]=1.Cl.[NH2:28][CH2:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:26][C:4]1[CH:3]=[C:2]([NH:28][CH2:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH:7]=[CH:6][C:5]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 23676156Sodium t-butoxideHCID 671119992-(4-Bromo-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 67111760HCID 67111760, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(4-bromo-2-fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine (76.8 mg, 0.181 mmol), tert-butyl 3-aminopropanoate hydrochloride (43 mg, 0.235 mmol), Pd2(dba)3 (4.1 mg, 4.5 μmol), Xantphos (10 mg, 18 μmol) and sodium tert-butoxide (45 mg, 0.469 mmol) in toluene (1.9 mL) was heated under argon at 80° C. for 18 h, then at 130° C. (microwave) for 30 min, then at 150° C. (microwave) for 30 min. The reaction mixture was then cooled to 25° C. and concentrated onto silica gel. Chromatographic purification (silica gel, 0-50% EtOAc/hexanes) furnished tert-butyl 3-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenylamino)-propanoate as a yellow solid. MS (ESI) m/z: Calculated: 489.2; Observed: 490.1 (M++1).

Workup

  1. waitat 150° C. (microwave) for 30 min
  2. temperatureThe reaction mixture was then cooled to 25° C.
  3. concentrationconcentrated onto silica gel
  4. customChromatographic purification (silica gel, 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-918712a5e9e3425d86fdfd58dfc0e605
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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