HCID 178424914, compound → HCID 178424915, compound

HRID 80853Notes

Reaction equation

HRID 80853 reaction equation
CC1(C)[O:6][C@@H:5]([CH2:7][O:8][C:9]2[C:10]3[CH2:29][N:28]([C:30]4[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[CH:32][C:31]=4[CH3:39])[CH2:27][CH2:26][C:11]=3[N:12]=[C:13]([C:15]3[C:23]([CH3:24])=[CH:22][CH:21]=[C:20]4[C:16]=3[C:17]([CH3:25])=[N:18][NH:19]4)[N:14]=2)[CH2:4][O:3]1>C(O)(C(F)(F)F)=O.O>[CH3:25][C:17]1[C:16]2[C:20](=[CH:21][CH:22]=[C:23]([CH3:24])[C:15]=2[C:13]2[N:14]=[C:9]([O:8][CH2:7][C@H:5]([OH:6])[CH2:4][OH:3])[C:10]3[CH2:29][N:28]([C:30]4[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[CH:32][C:31]=4[CH3:39])[CH2:27][CH2:26][C:11]=3[N:12]=2)[NH:19][N:18]=1

Participants

4

Reactant 1

HCID 178424914HCID 178424914, compound

Product 1

HCID 178424915HCID 178424915, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (S)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-2-(3,5-dimethyl-1H-indazol-4-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (20 mg, 0.037 mmol) in TFA (0.9 mL) and H2O (0.1 mL) was stirred at room temperature for 16 h. The reaction mixture was concentrated and the residue was partitioned between DCM and saturated aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with DCM. The organics were combined and concentrated. The residue was purified by reverse phase HPLC (C18, 10-100% acetonitrile in H2O with 0.1% NH4OH) to give (R)-3-((2-(3,5-dimethyl-1H-indazol-4-yl)-6-(5-isopropyl-2-methylphenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)propane-1,2-diol. 1H NMR (400 MHz, CD2Cl2) δ ppm 7.33 (d, J=8.46 Hz, 1H), 7.21 (d, J=8.59 Hz, 1H), 7.08 (d, J=7.96 Hz, 1H), 6.97 (d, J=1.52 Hz, 1H), 6.86 (dd, J=1.71, 7.77 Hz, 1H), 4.36-4.47 (m, 2H), 4.06 (s, 2H), 3.88-3.95 (m, 1H), 3.53-3.60 (m, 1H), 3.46-3.52 (m, 1H), 3.26 (t, J=5.68 Hz, 2H), 3.02-3.10 (m, 2H), 2.76-2.86 (m, 1H), 2.26 (s, 3H), 2.20 (s, 3H), 1.92 (s, 3H), 1.17 (d, J=6.95 Hz, 6H); MS (ESL) m/z 502.5 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was partitioned between DCM and saturated aqueous NaHCO3
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with DCM
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (C18, 10-100% acetonitrile in H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-8f5e2501d52a4523a8147088b19e0a7b
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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