Diisopropylethylamine → (9H-Fluoren-9-yl)methyl(R)-1-((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)ethylamino)-1-oxopropan-2-ylcarbamate

HRID 558152Notes

Reaction equation

HRID 558152 reaction equation
C(N(C(C)C)CC)(C)C.[N:10]1([CH2:15][CH2:16][NH:17][C:18]2[N:23]=[C:22]([C:24]3[S:28][C:27]4[C:29]([C:33]5[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=5[C@H:40]([NH2:42])[CH3:41])=[CH:30][CH:31]=[CH:32][C:26]=4[CH:25]=3)[C:21]([F:43])=[CH:20][N:19]=2)[CH:14]=[CH:13][N:12]=[N:11]1.[CH:44]1[C:56]2[CH:55]([CH2:57][O:58][C:59]([NH:61][C@@H:62]([C:64](Cl)=[O:65])[CH3:63])=[O:60])[C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[C:48]=2[CH:47]=[CH:46][CH:45]=1>O1CCOCC1.C(Cl)(Cl)Cl.C(O)(C)C>[N:10]1([CH2:15][CH2:16][NH:17][C:18]2[N:23]=[C:22]([C:24]3[S:28][C:27]4[C:29]([C:33]5[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=5[C@H:40]([NH:42][C:64](=[O:65])[C@H:62]([NH:61][C:59](=[O:60])[O:58][CH2:57][CH:55]5[C:54]6[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=6[C:48]6[C:56]5=[CH:44][CH:45]=[CH:46][CH:47]=6)[CH3:63])[CH3:41])=[CH:30][CH:31]=[CH:32][C:26]=4[CH:25]=3)[C:21]([F:43])=[CH:20][N:19]=2)[CH:14]=[CH:13][N:12]=[N:11]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11131317Fmoc-D-alanyl chlorideHCID 59272472(R)-N-(2-(1H-1,2,3-triazol-1-yl)ethyl)-4-(7-(2-(1-aminoethyl)-5-fluorophenyl)benzo[b]thiophen-2-yl)-5-fluoropyrimidin-2-amine

Product 1

HCID 86640663(9H-Fluoren-9-yl)methyl(R)-1-((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)ethylamino)-1-oxopropan-2-ylcarbamateYield 100.2%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

Add diisopropylethylamine (43 mg, 335 μmol) to a solution of (R)—N-(2-(1H-1,2,3-triazol-1-yl)ethyl)-4-(7-(2-(1-aminoethyl)-5-fluorophenyl)benzo[b]thiophen-2-yl)-5-fluoropyrimidin-2-amine (80 mg, 167 μmol), (9-fluorenyl methoxycarbonyl)-D-alanine-chloride (83 mg, 251 μmol) in 1,4-dioxane (5 mL). Stir the mixture at RT for 3 h. Dilute the mixture with chloroform/IPA (3/1, 100 mL), wash with water/aqueous saturated sodium chloride, dry over sodium sulfate, and concentrate in vacuo. Purify the crude product by FCC (10% methanol in DCM as elute) to give the title compound as a yellow solid (129 mg, 100%). MS (ES) m/z 770 [M+1]+.

Workup

  1. washwash with water/aqueous saturated sodium chloride
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate in vacuo
  4. customPurify the crude product
  5. washby FCC (10% methanol in DCM as elute)

Sources & evidence

ORD record
ord-9a08c34e1be44fbdaff41a7a62bb5bb5
Source dataset
uspto-grants-2011_11
Patent number
US08063035B2

Reaction notes

Loading…