Trifluoroacetic acid → HCID 178440683, compound

HRID 511654Notes

Reaction equation

HRID 511654 reaction equation
FC(F)(F)C(O)=O.[C:8]([C:12]1[CH:63]=[CH:62][C:15]2[NH:16][C:17]([CH2:19][CH2:20][CH:21]3[CH2:24][CH:23]([N:25]([CH2:30][C@@H:31]4[C@H:35]5[O:36]C(C)(C)[O:38][C@H:34]5[C@H:33]([N:41]5[C:45]6[N:46]=[CH:47][N:48]=[C:49]([NH:50]CC7C=CC(OC)=CC=7OC)[C:44]=6[CH:43]=[CH:42]5)[CH2:32]4)[CH2:26][CH:27]4[CH2:29][CH2:28]4)[CH2:22]3)=[N:18][C:14]=2[CH:13]=1)([CH3:11])([CH3:10])[CH3:9].C([SiH](CC)CC)C.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:50][C:49]1[C:44]2[CH:43]=[CH:42][N:41]([C@@H:33]3[CH2:32][C@H:31]([CH2:30][N:25]([CH:23]4[CH2:22][CH:21]([CH2:20][CH2:19][C:17]5[NH:16][C:15]6[CH:62]=[CH:63][C:12]([C:8]([CH3:9])([CH3:10])[CH3:11])=[CH:13][C:14]=6[N:18]=5)[CH2:24]4)[CH2:26][CH:27]4[CH2:29][CH2:28]4)[C@@H:35]([OH:36])[C@H:34]3[OH:38])[C:45]=2[N:46]=[CH:47][N:48]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 178491007HCID 178491007, compound

Product 1

HCID 178440683HCID 178440683, compoundYield 50.4%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Trifluoroacetic Acid (10 mL) added to a mixture of Water (1 mL) and 7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclopropylmethyl)amino)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-N-(2,4-dimethoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.52 g, 0.68 mmol) at RT. The reaction was stirred overnight at RT and Triethylsilane (0.22 mL, 1.4 mmol) was added. 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 the reaction stirred at RT for 1 hour. The mixture was filtered and the filter cake washed with 10 ml MeOH. The filtrate was concentrated and the resulting residue purified by flash chromatography (DCM I 7N NH3 in MeOH 90:10) to give the desired product (0.196 g) as an off white foam. MS (ESI+) for C33H45N7O2 m/z 572.6 [M+H]+; MS (ESI−) for C33H45N7O2 m/z 570.3 [M−H]−; HPLC purity >90% (ret. time, 2.850 min.) 1H NMR (400 MHz, d4-MeOH) δH 7.944 (s, 1H), 7.361 (s, 1H), 7.280-7.259 (m, 1H), 7.172-7.150 (m, 1H), 7.092-7.078 (m, 1H), 6.484-6.475 (d, J=3.6 Hz, 1H), 4.222-4.185 (m, 1H), 3.815-3.779 (m, 1H), 3.329 (m, 0.5H (methine of trans isomer)), 2.961 (m, 0.5H (methine of cis isomer), 2.745-2.627 (m, 3H), 2.503-2.450 (m, 1H), 2.301-2.187 (m, 5H), 2.036-1.890 (m, 2H), 1.793-1.776 (m, 3H), 1.529-1.385 (m, 2H), 1.246 (s, 9H), 0.808-0.739 (m, 1H), 0.394-0.362 (m, 2H), 0.012-0.013 (m, 2H). Retention time: 2.850 minutes. HPLC Conditions: Agilent Zorbax Exlipse XDB-C18 column, 4.6×50 mm (1.8 um packing), Solvent A—Water (0.1% TFA), Solvent B—Acetonitrile (0.07% TFA) 6 min gradient from 5 to 95% B; 1 min hold; then recycle.

Workup

  1. customThe volatiles were removed in vacuo
  2. customresulting residue
  3. stirringthe reaction stirred at RT for 1 hour
  4. filtrationThe mixture was filtered
  5. washthe filter cake washed with 10 ml MeOH
  6. concentrationThe filtrate was concentrated
  7. customthe resulting residue purified by flash chromatography (DCM I 7N NH3 in MeOH 90:10)

Sources & evidence

ORD record
ord-0236bb4ed9014121b5cbc8bf82e3f76b
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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