Hydrochloric Acid → 2,2,2-Trifluoro-N-(5-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-2,3-dihydro-1H-inden-2-yl)acetamide

HRID 1157622Notes

Reaction equation

HRID 1157622 reaction equation
O1C(C2C=C(N[C:13]3[N:18]=[C:17]([C:19]4[C:20]([C:28]5[CH:29]=[C:30]([NH:34][C:35](=[O:42])[CH2:36][C:37]6[S:38][CH:39]=[CH:40][CH:41]=6)[CH:31]=[CH:32][CH:33]=5)=[N:21][N:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=45)[CH:16]=[CH:15][N:14]=3)C=CC=2)=CN=C1.[NH2:43][C:44]1[CH:45]=[C:46]2[C:50](=[CH:51][CH:52]=1)[CH2:49][CH:48]([NH:53][C:54](=[O:59])[C:55]([F:58])([F:57])[F:56])[CH2:47]2.Cl.C(OCC)C>CC(O)C>[F:58][C:55]([F:56])([F:57])[C:54]([NH:53][CH:48]1[CH2:47][C:46]2[C:50](=[CH:51][CH:52]=[C:44]([NH:43][C:13]3[N:18]=[C:17]([C:19]4[C:20]([C:28]5[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][C:35](=[O:42])[CH2:36][C:37]6[S:38][CH:39]=[CH:40][CH:41]=6)[CH:29]=5)=[N:21][N:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=45)[CH:16]=[CH:15][N:14]=3)[CH:45]=2)[CH2:49]1)=[O:59]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 57737194N-{3-[3-(2-{[3-(1,3-Oxazol-5-yl)phenyl]amino}-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamideHCID 59511384N-(5-amino-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide

Product 1

HCID 577371772,2,2-Trifluoro-N-(5-{[4-(2-{3-[(2-thienylacetyl)amino]phenyl}pyrazolo-[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-2,3-dihydro-1H-inden-2-yl)acetamideYield 38%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (109 mg, 0.25 mmol) (see Example 2, step B) and N-(5-amino-2,3-dihydro-1H-inden-2-yl)-2,2,2-trifluoroacetamide (72 mg, 0.30 mmol) were combined in i-PrOH (2 mL) and 1M hydrochloric acid in diethyl ether (25 μL, 0.025 mmol) and heated at 180° C. in the microwave reactor for 20 min. The reaction product was concentrated and purified directly by silica gel flash column chromatography (30-100% EtOAc in hexanes). Purification yielded 61 mg (38%) of a brown oil. ES-LC/MS m/z=654 [M+H]+.

Workup

  1. concentrationThe reaction product was concentrated
  2. custompurified directly by silica gel flash column chromatography (30-100% EtOAc in hexanes)
  3. customPurification

Sources & evidence

ORD record
ord-d3955c791e62482da989988f0888ae39
Source dataset
uspto-grants-2010_10
Patent number
US07807673B2

Reaction notes

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