HCID 67313399, compound → HCID 67312776, compound

HRID 222043Notes

Reaction equation

HRID 222043 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([N:11]1[CH:19]=[C:18]2[C:13]([CH2:14][CH2:15][C:16]3[C:22]4=[C:23]([NH:27][C:28]5[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]6[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=6)=[C:30]([Cl:43])[CH:29]=5)[N:24]=[CH:25][N:26]=[C:21]4[S:20][C:17]=32)=[N:12]1)[CH:9]=[CH2:10]>C(OCC)(=O)C.[Pd]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:43][C:30]1[CH:29]=[C:28]([NH:27][C:23]2[N:24]=[CH:25][N:26]=[C:21]3[S:20][C:17]4[C:18]5[C:13]([CH2:14][CH2:15][C:16]=4[C:22]=23)=[N:12][N:11]([CH2:8][CH2:9][CH3:10])[CH:19]=5)[CH:33]=[CH:32][C:31]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([F:42])[CH:37]=1

Participants

4

Reactant 1

HCID 67313399HCID 67313399, compound

Product 1

HCID 67312776HCID 67312776, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-allyl-N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-6-amine trifluoroacetate (25.0 mg, 0.05 mmol) in ethyl acetate (1.50 mL) was added Pd/C (2.0 mg, 10%) under nitrogen. The reaction was stirred at rt under hydrogen atmosphere (balloon, 1 atm) for 4 h. The Pd/C residue was removed by filtering through a pad of celite and pad was washed with EtOAc (2×3 mL). The combined EtOAc layers were dried over sodium sulfate and the solvent was removed in vacuo. The residue was then separated by preparative HPLC to give (N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-2-propyl-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-6-amine trifluoroacetate (salt) (3.4 mg, 15%) as a yellow solid. 1H NMR (CD3CN) δ 8.33 (s, 1H), 7.82 (d, J=2.6 Hz, 1H), 7.65 (s, 1H), 7.49 (dd, J=2.3, 8.9 Hz, 1H), 7.45 (m, 1H), 7.33 (t, 1H), 7.28 (d, J=10 Hz, 1H), 7.14 (d, J=9 Hz, 1H), 7.12 (dt, 1H), 5.23 (s, 2H), 4.08 (t, 2H), 3.40 (t, 2H), 3.04 (t, 2H), 1.88 (m, 2H), 0.94 (t, 3H); LCMS RT=3.91 min, [M+H]+=520.1.

Workup

  1. customThe Pd/C residue was removed
  2. filtrationby filtering through a pad of celite and pad
  3. washwas washed with EtOAc (2×3 mL)
  4. dry with materialThe combined EtOAc layers were dried over sodium sulfate
  5. customthe solvent was removed in vacuo
  6. customThe residue was then separated by preparative HPLC

Sources & evidence

ORD record
ord-2993943949af4f0e989f0feb61c01029
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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