Toluene → HCID 67047279, compound

HRID 605871Notes

Reaction equation

HRID 605871 reaction equation
[NH2:1][C:2]1[C:3]([NH:19][C@H:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C@H:23]([O:30][Si:31]([C:44]([CH3:47])([CH3:46])[CH3:45])([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:22][CH2:21]2)=[N:4][C:5]([N:8]2[C:12]3[CH:13]=[C:14]([C:17]#[N:18])[CH:15]=[CH:16][C:11]=3[N:10]=[CH:9]2)=[N:6][CH:7]=1.[C:48]1(C)C=CC=C[CH:49]=1.COC(OC)N(C)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CCOC(C)=O>[Si:31]([O:30][C@H:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@H:20]([N:19]2[C:48]([CH3:49])=[N:1][C:2]3[C:3]2=[N:4][C:5]([N:8]2[C:12]4[CH:13]=[C:14]([C:17]#[N:18])[CH:15]=[CH:16][C:11]=4[N:10]=[CH:9]2)=[N:6][CH:7]=3)[CH2:21][CH2:22]1)([C:44]([CH3:47])([CH3:46])[CH3:45])([C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 78373Dimethylformamide dimethyl acetalHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 66970591HCID 66970591, compound

Product 1

HCID 67047279HCID 67047279, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A 50 ml round bottom flask was charged with 0.09 g (0.14 mmol) of 3-(5-amino-4-((1R,4R)-4-(tert-butyldiphenylsilyloxy)-1,2,3,4-tetrahydronaphthalen-1-ylamino)pyrimidin-2-yl)-3H-benzo[d]imidazole-5-carbonitrile (prepared from 3-(5-nitro-4-thiocyanatopyrimidin-2-yl)-3H-benzo[d]imidazole-5-carbonitrile and (1R,4R)-4-(tert-butyldiphenylsilyloxy)-1,2,3,4-tetrahydronaphthalen-1-amine via same procedure as in Example H, step 1 and Example B, step 3). 20 ml of toluene was then added, followed by 0.028 g (0.21 mmol) of N,N-dimethylformamide dimethylacetal, and a catalytic amount of pyridinium p-toluenesulfonate. The resulting mixture was stirred at 100° C. overnight (condenser used with flask). The mixture was cooled to room temp, diluted with 100 ml EtOAc and washed with approx 10 ml water. The organic layer was dried over MgSO4 and concentrated in vacuo, and purified by column chromatography (eluting with 1% MeOH in DCM), to give 0.06 g (65%) of the titled compound. Compound was single peak by HPLC and had an M+H of 660 by MS.

Workup

  1. temperatureThe mixture was cooled to room temp
  2. washwashed with approx 10 ml water
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. custompurified by column chromatography (eluting with 1% MeOH in DCM)

Sources & evidence

ORD record
ord-d6424027f6ed43a1b7658e3ce0e78e24
Source dataset
uspto-grants-2011_03
Patent number
US07915268B2

Reaction notes

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