1-methyl-1H-indazol-5-amine → HCID 11626469, compound

HRID 2375929Notes

Reaction equation

HRID 2375929 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].[CH3:24][N:25]1[C:33]2[C:28](=[CH:29][C:30]([NH2:34])=[CH:31][CH:32]=2)[CH:27]=[N:26]1>CCCCO>[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]([NH:34][C:30]4[CH:29]=[C:28]5[C:33](=[CH:32][CH:31]=4)[N:25]([CH3:24])[N:26]=[CH:27]5)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 27680321-methyl-1H-indazol-5-amineHCID 58709797tert-butyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 11626469HCID 11626469, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (638.1 mg, 1.906 mmol, 1 eq) and 1-methyl-1H-indazol-5-ylamine (567.4 mg, 3.855 mmol, 2 eq) in n-BuOH (26 mL) was stirred at 120° C. for 15 h. A white precipitate was filtered off, washed several times with MeOH, and dried under high vacuum, giving the title compound, as a white solid. The filtrate was adsorbed onto Hydromatrix, dry loaded, and purified by chromatography on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with MeOH:DCM 2%→4%→6%]. Fractions containing product were combined and concentrated in vacuo, affording a second batch of the title compound, as a brown solid. 1H NMR (400 MHz, DMSOd6): δ=1.44 (s, 9H), 2.43-2.53 (m, 2H), 3.57 (t, J=5.6 Hz, 2H), 4.03 (s, 5H), 6.38 (s, br, 1H), 6.76 (s, br, 1H), 8.60 (d, J=8.8 Hz, 1H), 7.69 (dd, J=8.8, 2.0 Hz, 1H), 8.01 (d, J=0.8 Hz, 1H), 8.26 (s, 1H), 8.39 (d, J=1.6 Hz, 1H), 9.34 (s, —NH), 11.91 (d, J=2.0 Hz, —NH). MS (ES+): m/z 446.07 (100) [MH+]. HPLC: tR=2.59 min (ZQ2000, polar—5 min).

Workup

  1. filtrationA white precipitate was filtered off
  2. washwashed several times with MeOH
  3. customdried under high vacuum

Sources & evidence

ORD record
ord-2f16da32e5e84f5097896483ac9c453c
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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