Water → HCID 178440684, compound

HRID 511651Notes

Reaction equation

HRID 511651 reaction equation
FC(F)(F)C(O)=O.O.[C:9]([C:13]1[CH:64]=[CH:63][C:16]2[NH:17][C:18]([CH2:20][CH2:21][CH:22]3[CH2:25][CH:24]([N:26]([CH2:31][C@@H:32]4[C@H:36]5[O:37]C(C)(C)[O:39][C@H:35]5[C@H:34]([N:42]5[C:46]6[N:47]=[CH:48][N:49]=[C:50]([NH:51]CC7C=CC(OC)=CC=7OC)[C:45]=6[CH:44]=[CH:43]5)[CH2:33]4)[CH:27]4[CH2:30][CH2:29][CH2:28]4)[CH2:23]3)=[N:19][C:15]=2[CH:14]=1)([CH3:12])([CH3:11])[CH3:10].C([SiH](CC)CC)C.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH2:51][C:50]1[C:45]2[CH:44]=[CH:43][N:42]([C@@H:34]3[CH2:33][C@H:32]([CH2:31][N:26]([CH:24]4[CH2:23][CH:22]([CH2:21][CH2:20][C:18]5[NH:17][C:16]6[CH:63]=[CH:64][C:13]([C:9]([CH3:10])([CH3:11])[CH3:12])=[CH:14][C:15]=6[N:19]=5)[CH2:25]4)[CH:27]4[CH2:28][CH2:29][CH2:30]4)[C@@H:36]([OH:37])[C@H:35]3[OH:39])[C:46]=2[N:47]=[CH:48][N:49]=1

Participants

8

Reactant 5

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 178491005HCID 178491005, compound

Product 1

HCID 178440684HCID 178440684, compoundYield 28.4%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 887MethanolSolvent

Procedure

Trifluoroacetic Acid (10 ml, 200 mmol) added to a mixture of Water (1 ml, 80 mmol) and 7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(cyclobutyl)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 (0.61 g, 0.80 mmol) at RT. The reaction was stirred o/n at RT and was quenched by the addition of Triethylsilane (0.26 ml, 1.6 mmol). The volatiles were removed in vacuo and resulting and the residue was taken up in MeOH (15 mls),500 mg K2CO3 and 8 drops of water were added and the reaction was stirred at RT for 1 hour. The mixture was filtered and the filter cake was washed with MeOH (10 ml). The filtrate was concentrated and the resulting residue purified by flash chromatogrpahy (DCM/7N NH3 in MeOH 90:10) to give the desired product (0.13 g) as a colorless foam. MS (ESI+) for C33H45N7O2 m/z 572.2 [M+H]+; MS (ESI−) for C33H45N7O2 m/z 570.2 [M−H]−; HPLC purity >90% (ret. time, 2.850 min.) 1H NMR (400 MHz, d4-MeOH) δH 8.083 (s, 1H), 7.492 (s, 1H), 7.412-7.392 (m, 1H), 7.309-7.286 (m, 1H), 7.220-7.205 (m, 1H), 6.620-6.610 (d, J=4.0 Hz, 1H), 4.321-4.283 (m, 1H), 3.888-3.848 (m, 1H), 3.505-3.417 (m, 0.5H (methine of trans isomer)), 3.231-3.147 (m, 0.5H) (methine of cis isomer)), 3.051-2.953 (m, 1H), 2.871-2.732 (m, 3H), 2.583-2.501 (m, 1H), 2.441-2.368 (m, 1H), 2.244-2.205 (m, 3H), 2.170-1.833 (m, 9H), 1.695-1.560 (m, 4H), 1.384 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-9f156d6845de4ed2b5c4b68823f9d938
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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