Cesium carbonate → (S)-1-{5-tert-Butyl-3-[2-(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-pyridin-3-ylmethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl}-pyrrolidin-3-ol

HRID 400932Notes

Reaction equation

HRID 400932 reaction equation
[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[C:16](Cl)=[N:17][CH:18]=[CH:19][CH:20]=3)[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].[N+:28]([C:31]1[C:36]2=[N:37][O:38][N:39]=[C:35]2[C:34]([NH2:40])=[CH:33][CH:32]=1)([O-:30])=[O:29].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[C:16]([NH:40][C:34]4[C:35]5=[N:39][O:38][N:37]=[C:36]5[C:31]([N+:28]([O-:30])=[O:29])=[CH:32][CH:33]=4)=[N:17][CH:18]=[CH:19][CH:20]=3)[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6018944-Amino-7-nitrobenzofurazanHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86295836(S)-1-[5-tert-Butyl-3-(2-chloro-pyridin-3-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol

Product 1

HCID 86683341(S)-1-{5-tert-Butyl-3-[2-(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-pyridin-3-ylmethyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl}-pyrrolidin-3-olYield 16.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-1-[5-tert-Butyl-3-(2-chloro-pyridin-3-ylmethyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]-pyrrolidin-3-ol (example 140) (5.30 mg, 13.7 μmol), 7-nitrobenzo[c][1,2,5]oxadiazol-4-amine (2.95 mg, 16.4 μmol), Pd2(dba)3 (1.25 mg, 1.37 μmol), xantphos (2.15 mg, 3.71 μmol) and Cs2CO3 (8.06 mg, 24.8 μmol) in dioxane (500 μl) was heated to 120° C. and stirred for 20 min. The crude material was filtered (celite), concentrated and purified by preparative HPLC eluting with a gradient formed from acetonitrile, water and NEt3. The product containing fractions were evaporated to yield 1.2 mg (16%) of the title compound as red solid. MS (m/e): 532.4 (MH+).

Workup

  1. filtrationThe crude material was filtered (celite)
  2. concentrationconcentrated
  3. custompurified by preparative HPLC
  4. washeluting with a gradient
  5. customformed from acetonitrile, water and NEt3
  6. additionThe product containing fractions
  7. customwere evaporated

Sources & evidence

ORD record
ord-fad00760678b44d79173ceee6428b695
Source dataset
uspto-grants-2014_06
Patent number
US08741906B2

Reaction notes

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