Ammonium Chloride → HCID 71209333, compound

HRID 1473153Notes

Reaction equation

HRID 1473153 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:26]=[C:25]([CH2:27][CH2:28][C:29]4[CH:30]=[C:31]([CH:36]=[CH:37][N:38]=4)[C:32](OC)=[O:33])[C:24]([C:39]([F:42])([F:41])[F:40])=[CH:23][N:22]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O.C[N:47](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Cl-].[NH4+]>C1COCC1.O.CO.CN(C=O)C>[C:32]([C:31]1[CH:36]=[CH:37][N:38]=[C:29]([CH2:28][CH2:27][C:25]2[C:24]([C:39]([F:41])([F:40])[F:42])=[CH:23][N:22]=[C:21]([NH:20][C:17]3[CH:18]=[CH:19][C:14]([CH:11]4[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9][CH2:10]4)=[CH:15][CH:16]=3)[N:26]=2)[CH:30]=1)(=[O:33])[NH2:47]

Participants

10

Reactant 5

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68282505HCID 68282505, compound

Product 1

HCID 71209333HCID 71209333, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)isonicotinate (I129) (70.0 mg, 0.120 mmol), and LiOH.H2O (15 mg, 0.36 mmol) in THF (5 mL), water (1 mL) and MeOH (0.5 mL) was stirred at room temperature for 4 hours. The volatiles were evaporated under reduced pressure to give a yellow solid which was dissolved in dry DMF (4 mL). HATU (133 mg, 0.350 mmol), DIPEA (60 μL, 0.034 mmol) and ammonium chloride (187 mg, 3.50 mmol) were added and the resulting mixture was stirred at room temperature overnight. The volatiles were evaporated under reduced pressure and the residue diluted with ethyl acetate. The resulting solution was washed with 10% aqueous NaHCO3, then the organic layer was dried (MgSO4) and volatiles removed by evaporation under reduced pressure. The residue was adsorbed onto silica gel and purified by chromatography (SiO2, 0-100% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I130) (50 mg, 50%) as a colourless solid; 1H NMR (400 MHz, CDCl3) δ 8.67 (dd, J=5.1, 0.7 Hz, 1H), 8.51 (s, 1H), 7.60 (s, 1H), 7.55 (s, 1H), 7.53 (d, J=8.6 Hz, 2H), 7.44 (dd, J=5.1, 1.6 Hz, 1H), 7.18 (d, J=8.5 Hz, 2H), 6.37-6.20 (m, 1H), 6.18-5.96 (m, 1H), 4.22 (s, 2H), 3.34 (tt, J=10.4, 5.0 Hz, 4H), 2.63 (s, 1H), 1.81 (d, J=12.7 Hz, 2H), 1.73 (s, 2H), 1.60 (dd, J=12.7, 4.1 Hz, 2H), 1.48 (s, 9H). LCMS Method C: rt 6.04 min; m/z 571.2 [M+1C, 569.2 [M−1]−, 515.2 [M−t-Bu+2]+.

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. customto give a yellow solid which
  3. customThe volatiles were evaporated under reduced pressure
  4. additionthe residue diluted with ethyl acetate
  5. washThe resulting solution was washed with 10% aqueous NaHCO3
  6. dry with materialthe organic layer was dried (MgSO4) and volatiles
  7. customremoved by evaporation under reduced pressure
  8. custompurified by chromatography (SiO2, 0-100% ethyl acetate/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-08d59de7f2cb41f4aeef602e7216ec33
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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