Acetic Acid → HCID 56967994, compound

HRID 1428258Notes

Reaction equation

[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](OCC2C=CC=CC=2)=O)[CH:4]2[CH2:18][CH2:19][N:20]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH:3]12.Br.C(O)(=O)C.C(Br)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([CH3:1])[CH:3]2[N:20]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:19][CH2:18][CH:4]12)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

Reactant 4

HCID 176Acetic Acid

HCID 260Hydrogen Bromide

HCID 7498Benzyl Bromide

HCID 68052115HCID 68052115, compound

Product 1

HCID 56967994HCID 56967994, compound

Procedure

To the product of Example 20 (40 mg, 0.102 mmol), was added HBr in acetic acid (1.5 mL, 0.102 mmol) and the reaction was stirred at room temperature for 2 hours before being concentrated in vacuo and azeotroped with heptanes (×2) and MeOH/heptanes (×1). The residue was taken up in methanol and passed through a Varian StratoSpheres™ SPE PL-HCO3 MP SPE resin. The solution was concentrated in vacuo and taken back up in MeOH (0.10 mL) and an additional amount of benzyl bromide (12.2 mg, 0.0714 mmol) was added and the reaction was stirred at 40° C. for 16 hours. The reaction was concentrated in vacuo and purified by mass triggered reverse phase HPLC. Lyophilization of the desired fractions gave the title product (TFA salt) as a white solid. LRMS calc'd for C21H26N5 [M+H]+, 348; found 348. Jak1 activity: ++.

Workup

concentrationbefore being concentrated in vacuo
customazeotroped with heptanes (×2) and MeOH/heptanes (×1)
concentrationThe solution was concentrated in vacuo
stirringthe reaction was stirred at 40° C. for 16 hours
concentrationThe reaction was concentrated in vacuo
custompurified by mass triggered reverse phase HPLC

Sources & evidence

ORD record: ord-710729c60da64531bdd6ba63fb3cbfc6
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08937077B2

Reaction notes

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