2,2,2-Trifluoroethyl trifluoromethanesulfonate → HCID 59239562, compound

HRID 1697958Notes

Reaction equation

HRID 1697958 reaction equation
C([O:8][C:9]1[N:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:23]=[C:24]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][C@@H:38]4[CH3:43])[C:25]4[CH2:31][CH2:30][N:29]([CH2:32][C:33]([F:36])([F:35])[F:34])[CH2:28][C:26]=4[N:27]=3)=[CH:18][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)C1C=CC=CC=1.Cl.C(OC1N=C(NC2C=CC(C3N=C(N4CCOC[C@@H]4C)C4CCNCC=4N=3)=CC=2)C=CC=1)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C.S(OCC(F)(F)F)(C(F)(F)F)(=O)=O>C(#N)C.C(OCC)(=O)C>[CH3:43][C@@H:38]1[N:37]([C:24]2[C:25]3[CH2:31][CH2:30][N:29]([CH2:32][C:33]([F:35])([F:34])[F:36])[CH2:28][C:26]=3[N:27]=[C:22]([C:19]3[CH:20]=[CH:21][C:16]([NH:15][C:13]4[NH:14][C:9](=[O:8])[CH:10]=[CH:11][CH:12]=4)=[CH:17][CH:18]=3)[N:23]=2)[CH2:42][CH2:41][O:40][CH2:39]1

Participants

7

Reactant 4

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonate2×HCID 81531DiisopropylethylamineHCID 59239408HCID 59239408, compoundHCID 67177348HCID 67177348, compound

Product 1

HCID 59239562HCID 59239562, compoundYield 110%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step 1—Synthesis of (S)-6-(benzyloxy)-N-(4-(4-(3-methylmorpholino)-7-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)pyridin-2-amine (pk). To a solution of (S)-6-(benzyloxy)-N-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)pyridin-2-amine hydrochloride salt (ms) (51 mg, 0.094 mmol) in Acetonitrile (1.0 mL) and N,N-Diisopropylethylamine (0.10 mL, 0.57 mmol) was added trifluoroethanol triflate (0.020 mL, 0.14 mmol) at room temperature, and the reaction mixture was microwaved at 140° C. for 30 minutes, followed by the addition of a second portion of Trifluoroethanol triflate (0.030 mL, 0.21 mmol). The resultant reaction mixture was microwaved at 140° C. for 20 minutes. The reaction mixture was diluted with Ethyl acetate, and washed by NaHCO3, water, and brine till pH 7. The orange organic solution was evaporated after dried over Magnesium sulfate. The residue was purified on a silica gel column to give the desired product (pk) (61 mg, 110% yield) as yellow powder: 1H NMR (500 MHz, CDCl3) δ 8.30 (d, J=8.4 Hz, 2H), 7.46 (m, 5H), 7.39 (t, J=7.5 Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 6.55 (s, 1H), 6.45 (d, J=7.8 Hz, 1H), 6.31 (d, J=7.9 Hz, 1H), 5.38 (s, 2H), 4.11 (m, 1H), 4.06-3.80 (m, 4H), 3.80-3.47 (m, 4H), 3.20 (q, J=9.4 Hz, 2H), 3.05-2.95 (m, 1H), 2.86 (m, 1H), 2.82-2.68 (m, 2H), 1.33 (d, J=6.6 Hz, 3H); LC-MS m/z=591 (M+H).

Workup

  1. customthe reaction mixture was microwaved at 140° C. for 30 minutes
  2. customThe resultant reaction mixture
  3. customwas microwaved at 140° C. for 20 minutes
  4. washwashed by NaHCO3, water, and brine till pH 7
  5. customThe orange organic solution was evaporated
  6. dry with materialafter dried over Magnesium sulfate
  7. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-92a8faf43565485598a4ff15acd1cde1
Source dataset
uspto-grants-2012_04
Patent number
US08163763B2

Reaction notes

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