Ammonium Chloride → HCID 11548129, compound

HRID 2240163Notes

Reaction equation

HRID 2240163 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.Br[C:30]1[CH:35]=[CH:34][C:33]([N:36]2[C:40]([C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([O:49][C@@H:50]4[CH2:54][CH2:53][O:52][CH2:51]4)[CH:42]=3)=[CH:39][CH:38]=[N:37]2)=[CH:32][CH:31]=1.[N:55]1([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][CH2:59][NH:58][CH2:57][CH2:56]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH4+].[Cl-]>O1CCCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[CH3:48][O:47][C:44]1[CH:45]=[CH:46][C:41]([C:40]2[N:36]([C:33]3[CH:34]=[CH:35][C:30]([N:58]4[CH2:57][CH2:56][N:55]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][CH2:59]4)=[CH:31][CH:32]=3)[N:37]=[CH:38][CH:39]=2)=[CH:42][C:43]=1[O:49][C@@H:50]1[CH2:54][CH2:53][O:52][CH2:51]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 68707916HCID 68707916, compound

Product 1

HCID 11548129HCID 11548129, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Into a 1-neck round-bottom flask was added 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (4.74 mg, 0.0120 mmol), 1-(4-bromophenyl)-5-{4-methoxy-3-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-1H-pyrazole (50.0 mg, 0.120 mmol), tert-butyl 1-piperazinecarboxylate (26.9 mg, 0.144 mmol) and tris(dibenzylideneacetone) dipalladium(0) (11.0 mg, 0.0120 mmol). The reaction was placed under an atmosphere of argon, 0.4 mL of 1.00 M lithium bis(trimethylsilyl)amide in tetrahydrofuran was added and the mixture was heated to 65° C. for 16 hours. After cooling to room temperature, 30 mL of saturated aqueous NH4Cl solution was added and the aqueous layer was extracted with 30 mL ethyl acetate. The separated organic layer was dried over sodium sulfate, filtered, and approximately 1 g silica gel was added and the mixture was evaporated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel eluting with 20% ethyl acetate in hexanes to yield tert-butyl 4-[4-(5-{4-methoxy-3-[(3R)-tetrahydrofuran-3-yloxy]phenyl}-1H-pyrazol-1-yl)phenyl]piperazine-1-carboxylate (21 mg, 34%) as a yellow oil. LC/MS (EI) tR 4.62 (Method C), m/z 521.3 (M++1). 1H NMR (CDCl3 300 MHz) δ 1.5 (s, 9H); 1.9 (m, 2H); 3.1 (m, 4H); 3.6 (m, 4H); 3.7-3.9 (m, 4H); 3.9 (s, 3H); 4.6 (m, 1H); 6.4 (s, 1 h); 6.6 (s, 1H); 6.9-7.1 (m, 4H); 7.2 (d, 2H); 7.6 (S, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe aqueous layer was extracted with 30 mL ethyl acetate
  3. dry with materialThe separated organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. additionapproximately 1 g silica gel was added
  6. customthe mixture was evaporated to dryness under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3cef7e3d0336448996d904db0adcdf59
Source dataset
uspto-grants-2010_05
Patent number
US07723348B2

Reaction notes

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