Potassium Carbonate → (2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate

HRID 510318Notes

Reaction equation

HRID 510318 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]=[CH:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:34][N:35]1[C:43]2[C:38](=[CH:39][C:40](B(O)O)=[CH:41][CH:42]=2)[CH:37]=[N:36]1.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.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1CC=CCCC=C1.C1CC=CCCC=C1.[Cl-].[Cl-].[Rh].[Rh]>[C:1]([O:5][C@@H:6]([C:11]1[C:25]([CH3:26])=[CH:24][C:14]2[N:15]=[C:16]([N:18]3[CH2:22][CH:21]([C:40]4[CH:39]=[C:38]5[C:43](=[CH:42][CH:41]=4)[N:35]([CH3:34])[N:36]=[CH:37]5)[CH2:20][C:19]3=[O:23])[S:17][C:13]=2[C:12]=1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 634876Binap, (A+-)-HCID 225589101-Methyl-1H-indazole-5-boronic acidHCID 86699848(S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzo[d]thiazol-6-yl)acetate

Product 1

HCID 86699849(2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate

Reagents, catalysts & solvents 2

HCID 6436379Rhodium, di-mu-chlorobis((1,2,5,6-eta)-1,5-cyclooctadiene)di-CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(2-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzo[d]thiazol-6-yl)acetate (12 mg, 0.025 mmol) in 1,4-dioxane/water (0.5 mL/50 μL) was added 1-methyl-1H-indazol-5-ylboronic acid (8 mg, 0.050 mmol), followed by chloro(1,5-cyclooctadiene)rhodium (I) dimer (1 mg), BINAP (5 mg), and potassium carbonate solution (2 N, 6 μL). The mixture was purged with nitrogen and heated at 80° C. for 24 hours. The mixture was diluted with EtOAc, and was washed with water and brine, dried with sodium sulfate and filtered. Concentration and purification by flash column chromatography (hexanes/EtOAc) gave (2S)-methyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(4-(1-methyl-1H-indazol-5-yl)-2-oxopyrrolidin-1-yl)benzo[d]thiazol-6-yl)acetate. LCMS-ESI+: calc'd for C33H33ClN4O4S: 617.2 (M+H+); Found: 617.2 (M+H+).

Workup

  1. customThe mixture was purged with nitrogen
  2. additionThe mixture was diluted with EtOAc
  3. washwas washed with water and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationConcentration and purification by flash column chromatography (hexanes/EtOAc)

Sources & evidence

ORD record
ord-ed3e9612ce8643dab73ad339e6d40980
Source dataset
uspto-grants-2015_08
Patent number
US09096586B2

Reaction notes

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