Cyclopropylamine → HCID 178521710, compound

HRID 1040020Notes

Reaction equation

HRID 1040020 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([NH:9][C:10]2[CH:11]=[C:12]([C:16]3[S:20][C:19]([C@H:21]4[CH2:26][CH2:25][C@H:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)=[N:18][CH:17]=3)[CH:13]=[CH:14][CH:15]=2)[N:4]=1.CN(C(ON1N=NC2[CH:43]=[CH:44][CH:45]=[N:46]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1(N)CC1>CN(C=O)C.C([O-])(O)=O.[Na+]>[CH:45]1([NH:46][C:27]([C@H:24]2[CH2:23][CH2:22][C@H:21]([C:19]3[S:20][C:16]([C:12]4[CH:13]=[CH:14][CH:15]=[C:10]([NH:9][C:5]5[N:4]=[C:3]([C:2]([F:1])([F:31])[F:30])[CH:8]=[CH:7][N:6]=5)[CH:11]=4)=[CH:17][N:18]=3)[CH2:26][CH2:25]2)=[O:28])[CH2:43][CH2:44]1

Participants

7

Reactant 4

HCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178525700HCID 178525700, compound

Product 1

HCID 178521710HCID 178521710, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

trans-4-[5-(3-{[4-(Trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexane-carboxylic acid (27 mg, 0.060 mmol) was dissolved in DMF (0.60 mL). To this solution was added HATU (24.04 mg, 0.063 mmol), DIPEA (0.063 mL, 0.361 mmol), followed by cyclopropylamine (3.44 mg, 0.060 mmol). The reaction was complete after stirring 1 hour at room temperature. The reaction mixture was diluted with saturated NaHCO3 and 2-Me-THF. The phases were separated and aqueous was extracted twice with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and were concentrated in vacuo. The residue was purified by column chromatography on silica gel (Combiflash, 0-50% EtOH in DCM) to yield trans-N-cyclopropyl-4-[5-(3-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxamide (10.9 mg, 0.022 mmol, 37.1% yield) as an off-white solid. MS APCI: [M+H]+ m/z 488.1. 1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H); 8.85 (d, J=4.8 Hz, 1H); 8.16 (s, 1H); 7.99 (s, 1H); 7.82 (d, J=4.2 Hz, 1H); 7.65 (d, J=8.0 Hz, 1H); 7.38 (t, J=7.9 Hz, 1H); 7.34-7.28 (m, 2H); 3.04-2.92 (m, 1H); 2.64-2.59 (m, 1H); 2.21-2.06 (m, 3H); 1.87-1.77 (m, 2H); 1.61-1.40 (m, 4H); 0.63-0.57 (m, 2H); 0.42-0.34 (m, 2H), rhSYK activity=+++

Workup

  1. customThe phases were separated
  2. extractionaqueous was extracted twice with ethyl acetate
  3. washThe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationwere concentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (Combiflash, 0-50% EtOH in DCM)

Sources & evidence

ORD record
ord-00e2cf57d8224a58bff0936f4cab47ff
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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