4-Aminopyrimidine → 1-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(Pyrimidin-4-yl)urea

HRID 1807754Notes

Reaction equation

HRID 1807754 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.C(N(C(C)C)C(C)C)C.ClC(Cl)(O[C:21](=[O:27])OC(Cl)(Cl)Cl)Cl.[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([N:38]2[CH2:43][CH2:42][N:41]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]([O:60][Si](C(C)(C)C)(C)C)([C:56]([F:59])([F:58])[F:57])[C:52]([F:55])([F:54])[F:53])=[CH:47][CH:46]=3)[CH2:40][CH2:39]2)=[O:37])=[CH:32][C:31]=1[F:68]>ClCCl>[F:68][C:31]1[CH:32]=[C:33]([C:36]([N:38]2[CH2:39][CH2:40][N:41]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([C:51]([OH:60])([C:52]([F:53])([F:54])[F:55])[C:56]([F:58])([F:59])[F:57])=[CH:47][CH:46]=3)[CH2:42][CH2:43]2)=[O:37])[CH:34]=[CH:35][C:30]=1[NH:29][C:21]([NH:7][C:4]1[CH:5]=[CH:6][N:1]=[CH:2][N:3]=1)=[O:27]

Participants

6

Reactant 4

HCID 689584-AminopyrimidineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 59175907(4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone

Product 1

HCID 445123941-(2-Fluoro-4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)benzyl)piperazine-1-carbonyl)phenyl)-3-(Pyrimidin-4-yl)ureaYield 83.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

Pyrimidin-4-amine (0.337 mmol, 0.032 g) and N-ethyl-N-isopropylpropan-2-amine (1.145 mmol, 0.189 mL, 0.148 g) were stirred in dichloromethane (2 mL) at room temperature. Triphosgene (0.125 mmol, 0.037 g) was added and the reaction stirred for 30 minutes. (4-Amino-3-fluorophenyl)(4-(4-(2-(tert-butyldimethylsilyloxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)benzyl)piperazin-1-yl)methanone (0.168 mmol, 0.1 g) was added and the reaction heated to 120° C. in the microwave for 10 minutes. The reaction mixture was washed with water and concentrated under reduced pressure. The resulting residue was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 5%) to afford the title compound (63 mg). MS (ESI) m/z 715.7 [M+H]+

Workup

  1. washThe reaction mixture was washed with water
  2. concentrationconcentrated under reduced pressure
  3. customThe resulting residue was purified by silica column chromatography (eluant dichloromethane/methanol 0% to 5%)

Sources & evidence

ORD record
ord-18109f56b1a0458cb43d6626a99f8f9e
Source dataset
uspto-grants-2013_01
Patent number
US08357679B2

Reaction notes

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