Water → HCID 178457357, compound

HRID 2040702Notes

Reaction equation

HRID 2040702 reaction equation
FC(F)(F)C(O)=O.O.COC1C=C(OC)C=CC=1C[NH:14][C:15]1[C:16]2[CH:23]=[CH:22][N:21]([C@H:24]3[C@H:31]4[C@H:27]([O:28]C(C)(C)[O:30]4)[C@@H:26]([CH2:34][N:35]([CH:56]([CH3:58])[CH3:57])[CH:36]4[CH2:39][CH:38]([CH2:40][CH2:41][C:42]5[NH:46][C:45]6[CH:47]=[CH:48][C:49]([O:51][C:52]([F:55])([F:54])[F:53])=[CH:50][C:44]=6[N:43]=5)[CH2:37]4)[CH2:25]3)[C:17]=2[N:18]=[CH:19][N:20]=1.C([SiH](CC)CC)C.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:14][C:15]1[C:16]2[CH:23]=[CH:22][N:21]([C@@H:24]3[CH2:25][C@H:26]([CH2:34][N:35]([CH:56]([CH3:57])[CH3:58])[CH:36]4[CH2:37][CH:38]([CH2:40][CH2:41][C:42]5[NH:46][C:45]6[CH:47]=[CH:48][C:49]([O:51][C:52]([F:53])([F:55])[F:54])=[CH:50][C:44]=6[N:43]=5)[CH2:39]4)[C@@H:27]([OH:28])[C@H:31]3[OH:30])[C:17]=2[N:18]=[CH:19][N:20]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 178491017HCID 178491017, compound

Product 1

HCID 178457357HCID 178457357, compoundYield 32.9%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 887MethanolSolvent

Procedure

Trifluoroacetic Acid (10 mL, 100 mmol) added to a mixture of Water (1 mL, 60 mmol) and N-(2,4-dimethoxybenzyl)-7-((3aS,4R,6R,6aR)-6-((isopropyl(3-(2-(5-(trifluoromethoxy)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)amino)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.91 g, 1.2 mmol) at RT. The reaction was stirred overnight at RT then quenched by the addition of Triethylsilane (0.37 mL, 2.3 mmol). The volatiles were removed in vacuo and resulting residue was taken up in MeOH (15 mls). 500 mgs of K2CO3 and 8 drops H2O were added and reaction stirred at RT for 1 hour. Mixture was filtered and filter cake washed with 10 mls MeOH. The filtrate was concentrated and the resulting residue purified by flash chromatography (DCM/7N NH3 in MeOH 90:10) to yield the desired product (0.232 g) as an off white foam. MS (ESI+) for C29H36F3N7O3 m/z 588.2 [M+H]+; MS (ESI−) for C29H36F3N7O3 m/z 586.2 [M−H]−; HPLC purity >90% (ret. time, 2.570 min.) 1H NMR (400 MHz, d4-MeOH) δH 8.082 & 8.079 (s, 1H, overlapping peaks due to cis and trans isomers), 7.554-7.524 (m, 1H), 7.414 (s, 1H), 7.225-7.209 (m, 1H), 7.155-7.127 (m, 1H), 6.618-6.609 (m, 1H), 4.363-4.323 (m, 1H), 3.976-3.932 (m, 1H), 3.606-3.524 (m, 0.5H (methine from trans isomer)), 3.156-3.110 (m, 0.5H (methine from cis isomer), 3.089-3.006 (m, 1H), 2.731-2.679 (m, 1H), 2.544-2.360 (m, 2H), 2.256-2.239 (m, 3H), 2.093-2.061 (m, 2H), 1.987-1.861 (m, 3H), 1.648-1.568 (m, 2H), 1.072-1.006 (m, 6H).

Workup

  1. customThe volatiles were removed in vacuo
  2. customresulting residue
  3. customreaction
  4. stirringstirred at RT for 1 hour
  5. filtrationMixture was filtered
  6. filtrationfilter cake
  7. washwashed with 10 mls MeOH
  8. concentrationThe filtrate was concentrated
  9. customthe resulting residue purified by flash chromatography (DCM/7N NH3 in MeOH 90:10)

Sources & evidence

ORD record
ord-07ad0f20c181405ca75b0cd8d2f60fcc
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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