Ammonium Chloride → 1-[2-(3-Cyanobenzyloxy)-5-fluoropyrimidin-4-yl]-3-propylthiourea

HRID 705584Notes

Reaction equation

HRID 705584 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([O:9][CH2:10][C:11]2[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=2)[C:14]#[N:15])[N:3]=1.[CH2:19]([N:22]=[C:23]=[S:24])[CH2:20][CH3:21].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>CN(C=O)C>[C:14]([C:13]1[CH:12]=[C:11]([CH:18]=[CH:17][CH:16]=1)[CH2:10][O:9][C:4]1[N:3]=[C:2]([NH:1][C:23]([NH:22][CH2:19][CH2:20][CH3:21])=[S:24])[C:7]([F:8])=[CH:6][N:5]=1)#[N:15]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 69403Propyl IsothiocyanateHCID 2733832Lithium HexamethyldisilazideHCID 57818679HCID 57818679, compound

Product 1

HCID 578190631-[2-(3-Cyanobenzyloxy)-5-fluoropyrimidin-4-yl]-3-propylthioureaYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a magnetically stirred mixture of 3-(4-amino-5-fluoropyrimidin-2-yloxymethyl)-benzonitrile (0.075 g, 0.31 mmol) and propylisothiocyanate (0.047 mL, 0.46 mmol) in dry DMF (1.5 mL) was added LiHMDS (1.0 M in THF, 0.31 ml, 0.31 mmol). The vial was capped and reaction was stirred for 8 h. Saturated aq NH4Cl (3 ml) was added to the vial and the mixture was stirred for 4 h. The heterogeneous mixture was filtered and the solid was washed with hot water, washed with hexanes, and dried under vacuum to give the title compound (0.055 g, 52%) as a pale-yellow solid: mp 163-165° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 10.38 (s, 1H), 8.47 (d, J=2.7 Hz, 1H), 7.90 (s, 1H), 7.82 (d, J=7.5 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.62 (t, J=7.7 Hz, 1H), 5.42 (s, 2H), 3.55 (dd, J=12.4, 6.8 Hz, 2H), 1.65-1.59 (m, 2H), 0.95 (t, J=7.5 Hz, 3H): HPLC-MS (ESI) m/z 346.3 (M+H)+, 344.2 (M−H)−.

Workup

  1. customThe vial was capped
  2. customreaction
  3. stirringwas stirred for 4 h
  4. filtrationThe heterogeneous mixture was filtered
  5. washthe solid was washed with hot water
  6. washwashed with hexanes
  7. customdried under vacuum

Sources & evidence

ORD record
ord-b3fb714904154266af748d59182976e6
Source dataset
uspto-grants-2015_11
Patent number
US09174970B2

Reaction notes

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