{1-[1-(4-fluoro-2-{2-[5-fluoro-2-(2-[1,2,3]triazol-1-yl-ethylamino)-pyrimidin-4-yl]-benzo[b]thiophen-7-yl}-phenyl)-ethylcarbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester → (R)-N-((R)-1-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)-4-fluorophenyl)ethyl)-2-aminopropanamide

HRID 558160Notes

Reaction equation

HRID 558160 reaction equation
C1C2C(COC(=O)[NH:17][CH:18]([C:20](=[O:55])[NH:21][CH:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[C:31]3[C:36]4[S:37][C:38]([C:40]5[C:45]([F:46])=[CH:44][N:43]=[C:42]([NH:47][CH2:48][CH2:49][N:50]6[CH:54]=[CH:53][N:52]=[N:51]6)[N:41]=5)=[CH:39][C:35]=4[CH:34]=[CH:33][CH:32]=3)[CH3:23])[CH3:19])C3C(=CC=CC=3)C=2C=CC=1>N1CCCCC1.C(Cl)(Cl)Cl.C(O)(C)C>[N:50]1([CH2:49][CH2:48][NH:47][C:42]2[N:41]=[C:40]([C:38]3[S:37][C:36]4[C:31]([C:25]5[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=5[C@H:22]([NH:21][C:20](=[O:55])[C@H:18]([NH2:17])[CH3:19])[CH3:23])=[CH:32][CH:33]=[CH:34][C:35]=4[CH:39]=3)[C:45]([F:46])=[CH:44][N:43]=2)[CH:54]=[CH:53][N:52]=[N:51]1

Participants

4

Reactant 1

HCID 66999424{1-[1-(4-fluoro-2-{2-[5-fluoro-2-(2-[1,2,3]triazol-1-yl-ethylamino)-pyrimidin-4-yl]-benzo[b]thiophen-7-yl}-phenyl)-ethylcarbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 59272443(R)-N-((R)-1-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)-4-fluorophenyl)ethyl)-2-aminopropanamideYield 78.6%

Reagents, catalysts & solvents 2

HCID 8082PiperidineSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

Dissolve {1-[1-(4-fluoro-2-{2-[5-fluoro-2-(2-[1,2,3]triazol-1-yl-ethylamino)-pyrimidin-4-yl]-benzo[b]thiophen-7-yl}-phenyl)-ethylcarbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester (129 mg, 167 μmol) in piperidine (5 mL). Stir the mixture at RT for 30 min and then dilute with chloroform/IPA (3/1, 100 mL). Wash the organic phase with water/aqueous saturated sodium chloride, dry over sodium sulfate, and concentrate in vacuo. Purify the crude product by FCC (10% methanol in DCM to chloroform/methanol/ammonium hydroxide (7/3/0.05) as a gradient to give the title compound as a yellow solid (72 mg, 78%). MS (ES) m/z 549 [M+1]+.

Workup

  1. washWash the organic phase with water/aqueous saturated sodium chloride
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate in vacuo
  4. customPurify the crude product by FCC (10% methanol in DCM to chloroform/methanol/ammonium hydroxide (7/3/0.05) as a gradient

Sources & evidence

ORD record
ord-9eff6e632311492a976aead0fd1d1108
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

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