p-Toluenesulfonic acid → (cis)-N-(4-(4-amino-3-fluoropiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amine

HRID 1256048Notes

Reaction equation

HRID 1256048 reaction equation
C(O)CCCC.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][C@H:28]([NH2:31])[C@H:27]([F:32])[CH2:26]2)=[CH:21][C:20]=1[O:33][CH3:34].Cl[C:36]1[N:41]=[C:40]([C:42]2[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[NH:44][CH:43]=2)[C:39]([Cl:51])=[CH:38][N:37]=1>>[NH2:31][C@H:28]1[CH2:29][CH2:30][N:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:36]3[N:41]=[C:40]([C:42]4[C:50]5[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=5)[NH:44][CH:43]=4)[C:39]([Cl:51])=[CH:38][N:37]=3)=[C:20]([O:33][CH3:34])[CH:21]=2)[CH2:26][C@H:27]1[F:32]

Participants

5

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 62761-PentanolHCID 566553763-(2,5-Dichloropyrimidin-4-yl)-1H-indole2×HCID 58071469(3R,4S)-1-(4-amino-3-methoxyphenyl)-3-fluoropiperidin-4-amine2×

Product 1

HCID 58071491(cis)-N-(4-(4-amino-3-fluoropiperidin-1-yl)-2-methoxyphenyl)-5-chloro-4-(1H-indol-3-yl)pyrimidin-2-amineYield 35.1%

Procedure

1-Pentanol (2 mL) was injected into a microwave vial charged with p-toluenesulfonic acid (0.180 g, 0.95 mmol), (3R,4S)-1-(4-amino-3-methoxyphenyl)-3-fluoropiperidin-4-amine (Intermediate 48) (0.091 g, 0.38 mmol), and 3-(2,5-dichloropyrimidin-4-yl)-1H-indole (Intermediate 2) (0.1 g, 0.38 mmol). The reaction was microwaved at 140° C. for 1 h. The solution was concentrated under reduced pressure. The crude residue was dissolved in DCM (15 mL) and washed with a sat. Na2CO3 solution. The organic layer was dried over Na2SO4, filtered, and the filtrate was concentrated to give a crude liquid. The crude material was purified using silica gel chromatography (2-10% MeOH and 1% NH4OH in DCM) to give the title product (0.062 g, 35.1%).

Workup

  1. customThe reaction was microwaved at 140° C. for 1 h
  2. concentrationThe solution was concentrated under reduced pressure
  3. dissolutionThe crude residue was dissolved in DCM (15 mL)
  4. washwashed with a sat. Na2CO3 solution
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customto give a crude liquid
  9. customThe crude material was purified

Sources & evidence

ORD record
ord-9aec4e12f73b4bccb42ead8018ee4632
Source dataset
uspto-grants-2013_06
Patent number
US08461170B2

Reaction notes

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