Acryloyl chloride → HCID 86721741, compound

HRID 1522100Notes

Reaction equation

HRID 1522100 reaction equation
Cl.[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([NH:9][CH2:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]2[OH:17])[C:4]=1[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.[C:40](Cl)(=[O:43])[CH:41]=[CH2:42]>C1COCC1>[NH2:2][C:3]1[N:8]=[CH:7][N:6]=[C:5]([NH:9][CH2:10][C@@H:11]2[CH2:16][CH2:15][N:14]([C:40](=[O:43])[CH:41]=[CH2:42])[CH2:13][C@H:12]2[OH:17])[C:4]=1[C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 71092775HCID 71092775, compound

Product 1

HCID 86721741HCID 86721741, compoundYield 3.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a round bottom flask containing (3S,4S)-4-{[6-Amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-methyl}-piperidin-3-ol hydrochloride (591.95 mg; 1.38 mmol; 1.00 eq.) and DIPEA (0.69 ml; 4.15 mmol; 5.00 eq.) in THF (30.00 ml) was slowly added acryloyl chloride (0.11 ml; 1.38 mmol; 1.00 eq.) in 1 mL THF over 1 h. The reaction mixture was concentrated and purified with using preparative HPLC. Fractions containing the desired product were combined and lyophilized overnight to afford 1-((3S,4S)-4-(((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)methyl)-3-hydroxypiperidin-1-yl)prop-2-en-1-one as a white solid (21.5 mg, 2.7%). HPLC purity: 99%. MS: m/z=446 [M+H]+. 1H NMR (CD3OD) δ 8.25 (s, 1H), 7.10-7.45 (m, 9H), 6.73 (dd, 1H), 6.34 (d, 1H), 5.77 (d, 1H), 4.5 (m, 1H), 4.03 (m, 1H), 3.62 (m, 1H), 3.50 (m, 1H), 3.25 (m, 1H), 3.01 (m, 1H), 2.57 (m, 1H), 1.71 (m, 2H), 1.19 (m, 1H).

Workup

  1. customover 1 h
  2. concentrationThe reaction mixture was concentrated
  3. custompurified
  4. additionFractions containing the desired product

Sources & evidence

ORD record
ord-6aacd28a22a446c894a1f5d41019055d
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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