Trifluoroacetic acid → HCID 178484133, compound

HRID 2040684Notes

Reaction equation

HRID 2040684 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:57]=[CH:56][C:12]2[NH:13][C:14]([CH2:16][CH2:17][CH:18]3[CH2:21][CH:20]([N:22]([CH2:24][C@@H:25]4[C@H:29]5[O:30]C(C)(C)[O:32][C@H:28]5[C@H:27]([N:35]5[C:39]6[N:40]=[CH:41][N:42]=[C:43]([NH:44]CC7C=CC(OC)=CC=7OC)[C:38]=6[CH:37]=[CH:36]5)[CH2:26]4)[CH3:23])[CH2:19]3)=[N:15][C:11]=2[CH:10]=1.C([SiH](CC)CC)C>O>[NH2:44][C:43]1[C:38]2[CH:37]=[CH:36][N:35]([C@@H:27]3[CH2:26][C@H:25]([CH2:24][N:22]([CH:20]4[CH2:19][CH:18]([CH2:17][CH2:16][C:14]5[NH:13][C:12]6[CH:56]=[CH:57][C:9]([Br:8])=[CH:10][C:11]=6[N:15]=5)[CH2:21]4)[CH3:23])[C@@H:29]([OH:30])[C@H:28]3[OH:32])[C:39]=2[N:40]=[CH:41][N:42]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 178491008HCID 178491008, compound

Product 1

HCID 178484133HCID 178484133, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Trifluoroacetic Acid (20 ml) added to a mixture of Water (2 ml) and 7-((3aS,4R,6R,6aR)-6-(((3-(2-(5-bromo-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(methyl)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 (0.9 g, 1 mmol) at RT. The reaction mixture was stirred for one hour, Triethylsilane (0.39 ml, 2.4 mmol) was added. The volatiles were removed in vacuo and resulting residue was purified twice by flash chromatography (DCM/7N NH3 in MeOH 87:13). The residue was taken up in MeOH/H2O (5:0.5 ml) and K2CO3 (100 mg) added. The mixture was stirred for 1 hour, then concentrated and purified by flash chromatography (DCM/7N NH3 in MeOH 87:13) to give the desired product (0.15 g) as an off-white foam/gum. cyclobutyl)(methyl)amino)methyl)cyclopentane-1,2-diol (0.15 g; 20%) as an off-white foam/gum. MS (ESI+) for C26H32BrN7O2 m/z 554.1 [M+H]+; MS (ESI−) for C26H32BrN7O2 m/z 552.1 [M−H]−; HPLC purity >90% (ret. time, 2.298 min.) 1HNMR (400 MHz, d4-MeOH) δH 8.080 (s, 1H), 7.652 (s, 1H), 7.425-7.403 (m, 1H), 7.342-7.7.312 (m, 1H), 7.232-7.217 (m, 1H), 6.620-6.611 (d, J=3.6 Hz, 1H), 4.358-4.318 (m, 1H), 3.928-3.888 (m, 1H), 3.099-3.039 (m, 0.5H (methine of trans isomer)), 2.898-2.829 (m, 2H), 2.777-2.726 (m, 0.5H (methine of cis isomer)), 2.580-2.529 (m, 1H), 2.453-2.397 (m, 2H), 2.307-2.141 (7H), 2.068-2.017 (m, 1H), 1.955-1.891 (m, 3H), 1.695-1.506 (m, 2H).

Workup

  1. customThe volatiles were removed in vacuo
  2. customresulting residue
  3. customwas purified twice by flash chromatography (DCM/7N NH3 in MeOH 87:13)
  4. additionK2CO3 (100 mg) added
  5. stirringThe mixture was stirred for 1 hour
  6. concentrationconcentrated
  7. custompurified by flash chromatography (DCM/7N NH3 in MeOH 87:13)

Sources & evidence

ORD record
ord-3ff32275945446568edf58e39a4945bf
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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