Pyridine → HCID 86721740, compound

HRID 1522099Notes

Reaction equation

HRID 1522099 reaction equation
Cl.[C@@H:2]12[CH:7]([CH2:8][NH:9][C:10]3[C:15]([C:16]4[CH:21]=[CH:20][C:19]([O:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[CH:18][CH:17]=4)=[C:14]([NH2:29])[N:13]=[CH:12][N:11]=3)[C@@H:6]1[CH2:5][NH:4][CH2:3]2.N1C=CC=CC=1.[C:36](Cl)(=[O:39])[CH:37]=[CH2:38].C(Cl)Cl>>[NH2:29][C:14]1[N:13]=[CH:12][N:11]=[C:10]([NH:9][CH2:8][CH:7]2[C@@H:6]3[C@H:2]2[CH2:3][N:4]([C:36](=[O:39])[CH:37]=[CH2:38])[CH2:5]3)[C:15]=1[C:16]1[CH:17]=[CH:18][C:19]([O:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:20][CH:21]=1

Participants

5

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 13140Acryloyl chlorideHCID 71092991HCID 71092991, compound

Product 1

HCID 86721740HCID 86721740, compoundYield 0.8%

Procedure

To a round bottom flask containing N-[(1S,5R)-1-(3-Aza-bicyclo[3.1.0]hex-6-yl)methyl]-5-(4-phenoxy-phenyl)-pyrimidine-4,6-diamine hydrochloride (259.68 mg; 0.63 mmol; 1.00 eq.) in pyridine (1.00 ml; 12.36 mmol; 19.52 eq.) was added acryloyl chloride (0.05 ml; 0.63 mmol; 1.00 eq.) in DCM (3.00 ml; 46.80 mmol; 73.88 eq.) over 1 h at 0° C. The reaction mixture was allowed to warm to room temperature and stirred overnight. It was concentrated and the crude product was subjected to preparative HPLC. Fractions containing the desired product were combined and lyophilized overnight to afford 1-((1R,5S)-6-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-3-azabicyclo[3.1.0]hexan-3-yl)prop-2-en-1-one as a white solid (2.1 mg, 0.6%). HPLC purity: 99%. MS: m/z=428[M+H]+. 1H NMR (CD3OD) δ 8.24 (s, 1H), 7.21-7.46 (m, 9H), 6.53 (m, 1H), 6.22 (m, 1H), 5.74 (m, 1H), 3.77 (m, 2H), 3.69 (m, 1H), 3.41 (m, 2H), 1.70 (m, 2H), 0.93 (m, 2H).

Workup

  1. concentrationIt was concentrated
  2. additionFractions containing the desired product
  3. waitlyophilized overnight

Sources & evidence

ORD record
ord-1212a6acf9ac4481805afb2202e02022
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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