Diisopropylethylamine → HCID 58709851, compound

HRID 2375862Notes

Reaction equation

HRID 2375862 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:24][N:25]1[C:29]2[N:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[N:26]1.N1CC=C(C2NC3N=CN=C(ON4C5=NC=CC=C5N=N4)C=3C=2)CC1.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.CCN(C(C)C)C(C)C>C(O)CCC.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:23][C:17]3[N:18]=[CH:19][N:20]=[C:21]([O:24][N:25]4[C:29]5=[N:30][CH:31]=[CH:32][CH:33]=[C:28]5[N:27]=[N:26]4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 181649HOAtHCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylateHCID 58710090HCID 58710090, compound

Product 1

HCID 58709851HCID 58709851, compound

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (11.5 mg, 0.0343 mmol, 1 eq) and 1-hydroxy-7-azabenzotriazole (HOAt) (5.6 mg, 0.041 mmol, 1.2 eq) in n-butanol (1 mL) was stirred at 80° C. for 15 h. Solid that had formed during the course of the reaction was filtered over a Hirsh funnel and washed with minimal n-butanol. The filtrate was concentrated in vacuo. To a solution of the solid (3-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-3H-[1,2,3]triazolo[4,5-b]pyridine) (6.4 mg, 0.015 mmol, 1 eq) in DMSO (1 mL), di-tert-butyldicarbonate (5.0 mg, 0.023 mmol, 1.5 eq) and DiPEA (20 μL, 0.1 mmol, 7 eq) were added and the reaction was stirred at rt for 2 h. This solution was combined with the concentrated filtrate and purified on the MDPS yielding the title compound. 1H NMR (400 MHz, MeOH-d4): δ=1.51 (s, 9H), 2.64 (s, br, 2H), 3.70 (s, br, 2H), 4.17 (s, br, 2H), 6.46 (s, br, 1H), 6.74 (s, 1H), 7.61 (dd, J=8.4, 4.4 Hz, 1H), 8.13 (s, 1H), 8.61 (d, J=8.0 Hz, 1H), 8.74 (d, J=4.4 Hz, 1H). MS (ES+): m/z 435.00 (62) [MH+]. HPLC: tR=3.36 min (ZQ2000, polar—5 min).

Workup

  1. customSolid that had formed during the course of the reaction
  2. filtrationwas filtered over a Hirsh funnel
  3. washwashed with minimal n-butanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified on the MDPS

Sources & evidence

ORD record
ord-4ba6c98009044ddca280696788c1a06e
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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