HCID 67818966, compound → 1-[3-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)urea

HRID 2284551Notes

Reaction equation

HRID 2284551 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:22][C@@H:23]2[C@@H:30]3[C@@H:26]([O:27]C(C)(C)[O:29]3)[C@H:25]([N:33]3[C:37]4[N:38]=[CH:39][N:40]=[C:41]([NH:42]CC5C=CC(OC)=CC=5OC)[C:36]=4[CH:35]=[CH:34]3)[O:24]2)[CH:19]([CH3:21])[CH3:20])=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>FC(F)(F)C(O)=O.O>[NH2:42][C:41]1[C:36]2[CH:35]=[CH:34][N:33]([C@@H:25]3[O:24][C@H:23]([CH2:22][N:18]([CH:19]([CH3:20])[CH3:21])[CH2:17][CH2:16][CH2:15][NH:14][C:12]([NH:11][C:8]4[CH:7]=[CH:6][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:10][CH:9]=4)=[O:13])[C@@H:30]([OH:29])[C@H:26]3[OH:27])[C:37]=2[N:38]=[CH:39][N:40]=1

Participants

4

Reactant 1

HCID 67818966HCID 67818966, compound

Product 1

HCID 569623361-[3-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)ureaYield 46.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

1-(4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)propyl)urea (1.07 g, 1.39 mmol) was dissolved in a mixture of trifluoroacetic acid (25 mL) and water (2.5 mL) which had been cooled at 0° C. and the resulting solution was stirred at 0° C. for 30 minutes, then warmed to room temperature. After 4 h, the reaction was found to be complete by HPLC. The reaction mixture was concentrated in vacuo and the residue was taken up in 25 mL MeOH (white slurry) and concentrated. This process was repeated three times and the resultant residue was placed under high vacuum. The material was taken up in 100 mL 10% MeOH/CH2Cl2 and washed with two 75 mL portions of sat NaHCO3 and 50 mL 1% aq Na2CO3. The organic phase was dried over Na2SO4, filtered and concentrated to yield a glass/solid. The crude material was purified by flash chromatography (100 g silica gel, 5-10% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (0.35 g, 46%) as a colorless glass: MS (ESI+) for C28H41N7O4 m/z 540.3 (M+H)+; (ESI−) for C28H41N7O4 m/z 538.3 (M−H)−, m/z 584.4 (M+HCO2)−; HPLC purity 98% (ret. time 2.86 min); 1H NMR (400 MHz, d4-MeOH) ppm 8.05 (s, 1H), 7.27 (d, J=3.73 Hz, 1H), 7.24 (m, 2H), 7.18 (m, 2H), 6.63 (d, J=3.73 Hz, 1H), 6.15 (d, J=4.77 Hz, 1H), 4.46 (t, J=5.08 Hz, 1H), 4.18 (t, J=5.39 Hz, 1H), 4.11 (m, 1H), 3.22 (m, 2H), 3.07 (m, 1H), 2.85 (m, 1H), 2.72 (m, 1H), 2.60 (t, J=6.43 Hz, 2H), 1.68 (m, 2H), 1.28 (s, 9H), 1.05 (d, J=6.63 Hz, 3H), 1.01 (d, J=6.43 Hz, 3H).

Workup

  1. temperaturewarmed to room temperature
  2. waitAfter 4 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. concentrationconcentrated
  5. washwashed with two 75 mL portions of sat NaHCO3 and 50 mL 1% aq Na2CO3
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto yield a glass/solid
  10. customThe crude material was purified by flash chromatography (100 g silica gel, 5-10% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-f07fb1588503434d934d69352d80ae85
Source dataset
uspto-grants-2015_09
Patent number
US09145438B2

Reaction notes

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