Trifluoroacetic acid → HCID 66970780, compound

HRID 1363165Notes

Reaction equation

HRID 1363165 reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[NH:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][C:21](=[O:37])[N:22]2[C@H:25]2[C:34]3[C:29](=[C:30]([F:36])[CH:31]=[C:32]([F:35])[CH:33]=3)[O:28][CH2:27][CH2:26]2)=[CH:18][N:17]=1.C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>C(Cl)Cl>[NH2:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[NH:15][C:16]1[N:24]=[C:23]2[C:19]([NH:20][C:21](=[O:37])[N:22]2[C@H:25]2[C:34]3[C:29](=[C:30]([F:36])[CH:31]=[C:32]([F:35])[CH:33]=3)[O:28][CH2:27][CH2:26]2)=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 66970577HCID 66970577, compound

Product 1

HCID 66970780HCID 66970780, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-4-(2,4-dimethoxybenzylamino)-3-(9-(6,8-difluorochroman-4-yl)-8-oxo-8,9-dihydro-7H-purin-2-ylamino)benzonitrile (230 mg) in DCM (5 mL) was treated with TFA (5 mL) and triethylsilane (1 mL) for 16 h. The mixture was concentrated in vacuo to provide the intermediate (R)-4-amino-3-(9-(6,8-difluorochroman-4-yl)-8-oxo-8,9-dihydro-7H-purin-2-ylamino)benzonitrile. The intermediate was dissolved in 5 mL THF and treated with 3 mL trimethylorthoformate followed by p-toluenesulfonic acid (3 mg). After 1 hour, the mixture was diluted with EtOAc (100 mL) and washed once with saturated aqueous sodium bicarbonate (100 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated in vacuo. Column chromatography (50→100% EtOAc/hexanes) provided 78 mg of the title compound. 1H-NMR (300 MHz, 5% CD3OD in CDCl3) δ 8.8 (s, 1H), 8.7 (s, 1H), 8.2 (s, 1H), 7.8 (d, 1H), 7.6 (dd, 1H), 6.8 (td, 1H), 6.4 (dd, 1H), 5.8 (dd, 1H), 4.6 (m, 1H), 4.4 (td, 1H), 2.9 (m, 1H), 2.3 (m, 1H).

Workup

  1. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-c7fe7602f13e4d67a83fc769a4cc9d5a
Source dataset
uspto-grants-2011_02
Patent number
US07884109B2

Reaction notes

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