1,2-Dichloroethane → Tert-butyl 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)benzoate

HRID 1410002Notes

Reaction equation

HRID 1410002 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21](O)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[NH2:30][C:31]1[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:33][CH:32]=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([NH:30][C:31]3[CH:43]=[CH:42][C:34]([C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])=[CH:33][CH:32]=3)=[O:22])[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 665513433-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid

Product 1

HCID 68379374Tert-butyl 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)benzoateYield 70%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

The mixture of 3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzoic acid (130 mg, 0.32 mmol), tert-butyl 4-aminobenzoate (185 mg, 0.96 mmol), EDC (122 mg, 0.64 mmol) and DMAP (78 mg, 0.64 mmol) in 10 mL of DMF was stirred at room temperature for 2 hours. Excess of DMF was removed under reduced pressure and the residue was dissolved in 100 mL of ethyl acetate, washed with brine (2×10 mL), dried over anhydrous sodium sulfate. The crude residue was purified by silica gel chromatography (200-300 mesh, eluting with ethyl acetate) to give tert-butyl 4-(3-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamido)benzoate (130 mg, 70%) as a white solid. 1H NMR (300 MHz, DMSO): δ 10.76 (s, 1H), 10.18 (s, 1H), 9.41 (s, 1H), 8.97 (s, 1H), 8.62 (d, 1H, J=8.1 Hz), 8.10 (d, 1H, J=7.8 Hz), 7.95 (s, 4H), 7.85 (s, 1H), 7.71 (t, 1H, J=7.7 Hz), 7.54 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 6.99 (d, 1H, J=9.0 Hz), 3.81 (s, 3H), 3.75 (s, 3H), 1.57 (s, 3H). LC-MS: 584 [M+H]+, tR=1.78 min. HPLC: 98.03% at 214 nm, 98.38% at 254 nm, tR=7.05 min.

Workup

  1. customExcess of DMF was removed under reduced pressure
  2. dissolutionthe residue was dissolved in 100 mL of ethyl acetate
  3. washwashed with brine (2×10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe crude residue was purified by silica gel chromatography (200-300 mesh, eluting with ethyl acetate)

Sources & evidence

ORD record
ord-90f2ad4542b34ec2bf2f6025893c066b
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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