Dimethylformamide → HCID 86664033, compound

HRID 712319Notes

Reaction equation

HRID 712319 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH2:34][CH3:35])([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.C(Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([SiH](CC)CC)C.C(N(CC)CC)C.[C]=O.CN([CH:87]=[O:88])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:32]([O:31][C:29]([C:26]1([CH2:34][CH3:35])[CH2:27][CH2:28][N:23]([C:20]2[N:19]=[CH:18][C:17]([C:4]3[CH:3]=[C:2]([CH:87]=[O:88])[C:10]4[S:9][C:8]([NH:11][C:12](=[O:16])[NH:13][CH2:14][CH3:15])=[N:7][C:6]=4[CH:5]=3)=[CH:22][N:21]=2)[CH2:24][CH2:25]1)=[O:30])[CH3:33]

Participants

10

Reactant 7

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 812191,3-Bis(diphenylphosphino)propaneHCID 86664034HCID 86664034, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 86664033HCID 86664033, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
75 °C

Procedure

A medium pressure reaction vessel was charged with the following reagents and solvent(s): Ethyl 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylate (2.54 g, 4.52 mmol), palladium acetate (102 mg, 0.452 mmol), Pd(dppf)Cl2.CH2Cl2 (200 mg, 0.2 mmol), 3-diphenylphosphanylpropyl(diphenyl)phosphane (200 mg, 0.5 mmol), triethylsilane (2.3 mL, 14 mmol), triethylamine (1.3 mL, 9.05 mmol) in DMF (35 mL). The mixture was pressurised to 100 psi of carbon monoxide and heated at 75° C. overnight. The reaction was filtered through a 0.4 micron filter, and the majority of the DMF was removed in vacuo. Partitioning the crude mixture between DCM (100 mL) and washing with water (100 mL) followed by sat. aq. brine (100 mL) afforded a dark red syrup upon drying over MgSO4 and removal of the volatiles. Subjecting the residue to flash chromatography (Grace 80 g, 0-10% DCM/MeOH) yielded 1.85 g (80% yield) of the product as a yellow solid. 1HNMR (CDCl3) δ 10.20 (d, J=12.8 Hz, 1H), 8.65 (d, J=9.9 Hz, 2H), 8.11 (d, J=1.6 Hz, 1H), 7.86 (d, J=1.7 Hz, 1H), 4.58 (dt, J=13.7, 3.4 Hz, 2H), 4.23 (qd, J=7.1, 3.4 Hz, 2H), 3.57-3.41 (m, 2H), 3.28-3.10 (m, 2H), 2.26 (d, J=13.2 Hz, 2H), 1.61 (dt, J=7.5, 5.7 Hz, 4H), 1.52-1.39 (m, 2H), 1.31 (td, J=7.2, 3.6 Hz, 6H), 0.91-0.84 (m, 3H). MS: 511.0 [M+H]+.

Workup

  1. customA medium pressure reaction vessel
  2. filtrationThe reaction was filtered through a 0.4 micron
  3. filtrationfilter
  4. customthe majority of the DMF was removed in vacuo
  5. customPartitioning the crude mixture between DCM (100 mL)
  6. washwashing with water (100 mL)
  7. customafforded a dark red syrup
  8. dry with materialupon drying over MgSO4 and removal of the volatiles

Sources & evidence

ORD record
ord-bce6a7e7310047d6b8c8fd8e2ec800c8
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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