4-(Hydroxymethyl)phenylacetic acid → 2-[3-(hydroxymethyl)phenyl]-N-{5-[(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)carbonyl]pyridin-3-yl}acetamide

HRID 82235Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.OC[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][C:31]([OH:33])=O)=[CH:26][CH:25]=1.CN([C:37]([O:41]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>N1C=CC=CC=1>[OH:41][CH2:37][C:29]1[CH:28]=[C:27]([CH2:30][C:31]([NH:1][C:2]2[CH:7]=[N:6][CH:5]=[C:4]([C:8]([C:10]3[C:18]4[CH:17]=[N:16][CH:15]=[N:14][C:13]=4[N:12]([CH:19]([CH3:21])[CH3:20])[CH:11]=3)=[O:9])[CH:3]=2)=[O:33])[CH:26]=[CH:25][CH:24]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of (5-aminopyridin-3-yl)(7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)methanone (Preparation 95, 250 mg, 0.89 mmol), [4-(hydroxymethyl)phenyl]acetic acid (177 mg, 1.06 mmol) and HATU (505 mg, 1.33 mmol) in pyridine (7 mL) was stirred at 50° C. for 3 hours, then at room temperature for 18 hours. The mixture was concentrated in vacuo and azeotroped with toluene. The residue was purified by column chromatography using silica gel (gradient of dichloromethane to dichloromethane/methanol (10:1 to 9:1) to afford the title compound as a gum. This material was dissolved in a 9:1 mixture of dichloromethane/methanol (1.5 mL) and added dropwise to diethyl ether (100 mL), the resulting precipitate was filtered off and dried in vacuo to afford the title compound as a white solid, 412 mg, which was used crude in subsequent reactions.

Workup

waitat room temperature for 18 hours
concentrationThe mixture was concentrated in vacuo
customazeotroped with toluene
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-369d1fb3547841adbdd9510a17d47158
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846698B2

Reaction notes

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