Trifluoroacetic acid → HCID 178464372, compound

HRID 2040681Notes

Reaction equation

HRID 2040681 reaction equation
FC(F)(F)C(O)=O.[C:8]([C:12]1[CH:61]=[CH:60][C:15]2[NH:16][C:17]([CH2:19][CH2:20][CH:21]3[CH2:24][CH:23]([N:25]([CH2:28][C@@H:29]4[C@H:33]5[O:34]C(C)(C)[O:36][C@H:32]5[C@H:31]([N:39]5[C:43]6[N:44]=[CH:45][N:46]=[C:47]([NH:48]CC7C=CC(OC)=CC=7OC)[C:42]=6[CH:41]=[CH:40]5)[CH2:30]4)[CH2:26][CH3:27])[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>[NH2:48][C:47]1[C:42]2[CH:41]=[CH:40][N:39]([C@@H:31]3[CH2:30][C@H:29]([CH2:28][N:25]([CH:23]4[CH2:22][CH:21]([CH2:20][CH2:19][C:17]5[NH:16][C:15]6[CH:60]=[CH:61][C:12]([C:8]([CH3:10])([CH3:9])[CH3:11])=[CH:13][C:14]=6[N:18]=5)[CH2:24]4)[CH2:26][CH3:27])[C@@H:33]([OH:34])[C@H:32]3[OH:36])[C:43]=2[N:44]=[CH:45][N:46]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 178464371HCID 178464371, compound

Product 1

HCID 178464372HCID 178464372, compoundYield 22.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Trifluoroacetic Acid (20 mL) was added to a mixture of Water (2 mL) and 7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(ethyl)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 (0.85 g, 1.2 mmol) at RT. The reaction was allowed to proceed for one hour at which time Triethylsilane (0.37 mL, 2.3 mmol) was added. The volatiles were removed in vacuo and resulting residue was taken up in MeOH (3 mls), 1 ml of K2CO3 (saturated) was added and reaction stirred at RT for 1 hour. The mixture was partitioned between H2O and DCM/MeOH (9:1). The aqueous layer was extracted (3×) and the combined organics dried with MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (DCM/7N NH3 in MeOH 90:10) to yield the desired product (0.150 g) as an off white foam. MS (ESI+) for C31H43N7O2 m/z 546.3 [M+H]+; MS (ESI−) for C31H43N7O2 m/z 544.3 [M−H]−; HPLC purity >91% (ret. time, 2.734 min.) 1H NMR (400 MHz, d4-MeOH) δH 8.081 (s, 1H), 7.493 (s, 1H), 7.414-7.393 (m, 1H), 7.291-7.266 (m, 1H), 7.215-7.202 (m, 1H), 6.619-6.609 (d, J=4.0 Hz, 1H), 4.345-4.312 (m, 1H), 3.923-3.885 (m, 1H), 2.994-2.915 (m, 0.5 H (methine of trans isomer)), 2.860-2.793 (m, 214), 2.701-2.578 (m, 3H), 2.501-2.380 (m, 2H), 2.259-2.234 (m, 2H), 2.109-2.008 (m, 314), 1.920-1.880 (m, 3H), 1.658-1.499 (m, 231), 1.364 (s, 9H), 1.036-0.991 (m, 3H). Retention time: 2.734 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. additionwas added
  2. customThe volatiles were removed in vacuo
  3. customresulting residue
  4. customreaction
  5. customThe mixture was partitioned between H2O and DCM/MeOH (9:1)
  6. extractionThe aqueous layer was extracted (3×)
  7. dry with materialthe combined organics dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by flash chromatography (DCM/7N NH3 in MeOH 90:10)

Sources & evidence

ORD record
ord-a01f9bc0f67a40dcb9fee6674658eeca
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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