Water → HCID 178484135, compound

HRID 2040706Notes

Reaction equation

HRID 2040706 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@H:23]4[C@H:19]([O:20]C(C)(C)[O:22]4)[C@@H:18]([CH2:26][N:27]([CH3:47])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]5[NH:38][C:37]6[CH:39]=[CH:40][C:41]([CH:43]7[CH2:46][O:45][CH2:44]7)=[CH:42][C:36]=6[N:35]=5)[CH2:29]4)[CH2:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.FC(F)(F)C(O)=O.O>>[NH2:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@@H:16]3[CH2:17][C@H:18]([CH2:26][N:27]([CH3:47])[CH:28]4[CH2:31][CH:30]([CH2:32][CH2:33][C:34]5[NH:38][C:37]6[CH:39]=[CH:40][C:41]([CH:43]7[CH2:44][O:45][CH2:46]7)=[CH:42][C:36]=6[N:35]=5)[CH2:29]4)[C@@H:19]([OH:20])[C@H:23]3[OH:22])[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

4

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 178491010HCID 178491010, compound

Product 1

HCID 178484135HCID 178484135, compoundYield 43.8%

Conditions

Temperature
0 °C

Procedure

N-(2,4-dimethoxybenzyl)-7-((3aS,4R,6R,6aR)-2,2-dimethyl-6-((methyl(3-(2-(5-(oxetan-3-yl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (115 mg, 0.159 mmol) was dissolved in a mixture of Trifluoroacetic Acid (4.00 ml, 51.9 mmol) and Water (0.40 ml, 22 mmol) which had been pre-cooled at 0° C. in an ice bath. The solution was stirred at 0° C. for 2 h, the reaction mixture was allowed to warm to RT. After 1 the reaction mixture was concentrated in vacuo. The residue was taken up in 6 ml MeOH, concentrated and the process was repeated twice. The resultant residue was placed on high vacuum. The crude residue was diluted with 2 ml MeOH, treated with 140 mg K2CO3 and 10 drops of H2O and allowed to stir at RT until the solution was basic by pH paper. The solution was filtered through a fine frit and the solids washed with MeOH. The filtrate was concentrated to a solid that was placed on high vacuum overnight. The crude material was purified by prep TLC on two 20 cm×20 cm×1.0 mm prep TLC plate, eluting with 14% 7N NH3 in CH3OH/CH2Cl2 to give the product as a colorless glass (37 mg) 1H NMR (400 MHz, MeOD) δH ppm 8.06 (s, 1 H), 7.52 (br. s., 1 H), 7.48 (d, J=8.29 Hz, 1 H), 7.28 (m, 1 H), 7.20 (t, J=3.42 Hz, 1 H), 6.60 (d, J=3.52 Hz, 1 H), 5.12 (m, 2 H), 4.80 (m, 2 H), 4.38 (m, 1 H), 4.32 (m, 1 H), 3.89 (q, J=5.60 Hz, 1 H), 3.04 (m, 1 H), 2.85 (m, 2 H), 2.70 (m, 1 H), 2.52 (m, 1 H), 2.41 (m. 2 H), 2.27 (dd, J=10.99, 6.63 Hz, 2 H), 2.19 (s, 3 H), 2.17 (s, 3 H), 2.14 (m, 1 H), 2.03 (d, J=7.88 Hz, 1 H), 1.91 (m, 3 H), 1.62 (m, 1 H), 1.51 (m, 1 H).

Workup

  1. temperatureto warm to RT
  2. concentrationAfter 1 the reaction mixture was concentrated in vacuo
  3. concentrationconcentrated
  4. additionThe crude residue was diluted with 2 ml MeOH
  5. additiontreated with 140 mg K2CO3 and 10 drops of H2O
  6. stirringto stir at RT until the solution
  7. filtrationThe solution was filtered through a fine frit
  8. washthe solids washed with MeOH
  9. concentrationThe filtrate was concentrated to a solid
  10. customthat was placed on high vacuum overnight
  11. customThe crude material was purified by prep TLC on two 20 cm×20 cm×1.0 mm prep TLC plate
  12. washeluting with 14% 7N NH3 in CH3OH/CH2Cl2

Sources & evidence

ORD record
ord-b78b2e5be33a4309be70c07a28a73575
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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