Dimethylformamide → HCID 57812467, compound

HRID 911995Notes

Reaction equation

HRID 911995 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:18]=[C:17]([C:19]3[C:23]4[CH:24]=[N:25][C:26]([NH2:40])=[C:27]([O:28][C@@H:29]([C:31]5[C:36]([Cl:37])=[CH:35][CH:34]=[C:33]([F:38])[C:32]=5[Cl:39])[CH3:30])[C:22]=4[O:21][C:20]=3Br)[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:42][N:43](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:40][C:26]1[N:25]=[CH:24][C:23]2[C:19]([C:17]3[CH:16]=[N:15][N:14]([CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[CH:18]=3)=[C:20]([C:42]#[N:43])[O:21][C:22]=2[C:27]=1[O:28][C@@H:29]([C:31]1[C:36]([Cl:37])=[CH:35][CH:34]=[C:33]([F:38])[C:32]=1[Cl:39])[CH3:30]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 57812632HCID 57812632, compound

Product 1

HCID 57812467HCID 57812467, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
150 °C

Procedure

A mixture of [4-(4-{6-amino-2-bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-furo[3,2-c]pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (20.0 mg, 0.0299 mmol), zinc cyanide (4.2 mg, 0.036 mmol) and Pd(PPh3)4 (3 mg, 0.003 mmol) in DMF (1 mL) was degassed and refilled with nitrogen (3×). The reaction was heated at 150° C. using a microwave reactor for 2 min. The solution was passed through a PL-Thiol SPE cartridge to remove metals. The material was then dissolved in dioxane and EtOH, charged with 4M HCl in Dioxane (0.2 mL) and stirred at rt for 4 h. The solution was concentrated in vacuo, redissolved in DMF (0.5 mL) and purified via HPLC. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.93 (d, J=6.8 Hz, 3H), 2.30-2.40 (m, 4H), 3.18-3.26 (m, 2H), 3.59 (d, J=13.4 Hz, 2H), 4.64-4.71 (m, 1H), 6.43 (q, J=6.8 Hz, 1H), 7.21-7.27 (m, 1H), 7.42 (dd, J=9.0, 4.9 Hz, 1H), 8.11 (s, 1H), 8.33-8.39 (m, 2H). MS (ES+): m/z 515.06/517.07 (100/68) [MH+]. HPLC: tR=2.78 min (ZQ2, polar—5 min).

Workup

  1. customwas degassed
  2. additionrefilled with nitrogen (3×)
  3. customfor 2 min
  4. customto remove metals
  5. dissolutionThe material was then dissolved in dioxane
  6. additionEtOH, charged with 4M HCl in Dioxane (0.2 mL)
  7. concentrationThe solution was concentrated in vacuo
  8. dissolutionredissolved in DMF (0.5 mL)
  9. custompurified via HPLC
  10. additionThe fractions containing the pure product
  11. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-b3590b3da5c944fab20b783387c8ecf4
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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