Dimethylacetamide → HCID 73442863, compound

HRID 928852Notes

Reaction equation

HRID 928852 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:20]3[N:24]([CH3:25])[C:23]([CH3:26])=[N:22][CH:21]=3)([C:14]3[N:18]([CH3:19])[N:17]=[N:16][CH:15]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:27][CH3:28])[C:3]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C[C:75]([N:77](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Zn].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]>[CH3:25][N:24]1[C:20]([C:12]([OH:13])([C:14]2[N:18]([CH3:19])[N:17]=[N:16][CH:15]=2)[C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[C:4]([O:27][CH3:28])[C:3]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:37])([F:38])[F:39])=[CH:32][CH:31]=2)=[C:2]3[C:75]#[N:77])=[CH:21][N:22]=[C:23]1[CH3:26]

Participants

7

Reactant 3

HCID 31374DimethylacetamideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 74221264HCID 74221264, compound

Product 1

HCID 73442863HCID 73442863, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
125 °C

Procedure

(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol (370 mg, 0.66 mmol, Example 80A), zinc cyanide (147 mg, 1.26 mmol), X-phos (64.5 mg, 0.14 mmol), zinc powder (12 mg, 0.19 mmol) tris(dibenzylideneacetone)dipalladium (0), (Pd2(dba)3, 98 mg, 0.11 mmol) were added to a large microwave vial, then DMA (8 mL, degassed with argon) was added and the vial was sealed and evacuated. The mixture was heated to 125° C. in an aluminum heating mantle (for how long?). The mixture was filtered through a Celite® pad while still warm, rinsed with EtOAc-MeOH (10:1) and concentrated under vacuum providing a brown oil. The crude material was purified by RP-HPLC to give the title compound as an off white solid. MS m/e 548.2 [M+H]+. 1H NMR (500 MHz, CDCl3) δ ppm 8.19 (s, 1H), 7.87 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.42 (apparent d, 8.1 Hz, 3H), 7.3-7.4 (m, 1H) 6.41 (s, 1H), 4.41-4.26 (m, 2H), 4.10 (s, 3H), 3.90 (s, 3H), 3.64 (s, 3H), 2.58 (s, 3H). The racemic material was separated into its individual enantiomers using the following conditions: Chiralpak IA SFC column (5 u), 85% hexane: 15% EtOH (containing 0.2% Et3N) to provide the two enantiomers. The first eluting enantiomer was Example 81B and the second eluting enantiomer was Example 81C.

Workup

  1. customthe vial was sealed
  2. customevacuated
  3. filtrationThe mixture was filtered through a Celite® pad
  4. temperaturewhile still warm
  5. washrinsed with EtOAc-MeOH (10:1)
  6. concentrationconcentrated under vacuum
  7. customproviding a brown oil
  8. customThe crude material was purified by RP-HPLC

Sources & evidence

ORD record
ord-74f84683c9ed43ae974bfdb6adfdb7ec
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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