Water → HCID 178440684, compound

HRID 2040691Notes

Reaction equation

HRID 2040691 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 chromatography (DCM/7N NH3 in MeOH 90:10) to give the desired product (0.13 g) as a colorless foam. MS (EST+) 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 chromatography (DCM/7N NH3 in MeOH 90:10)

Sources & evidence

ORD record
ord-e515105c7c7f4b0b9e84b9b0eaff4f73
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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