Propiolic Acid → HCID 86721742, compound

HRID 1522101Notes

Reaction equation

HRID 1522101 reaction equation
[C:1](O)(=[O:4])[C:2]#[CH:3].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(C(C)C)C(C)C)C.Cl.[NH2:31][C:32]1[N:37]=[CH:36][N:35]=[C:34]([NH:38][CH2:39][C@@H:40]2[CH2:45][CH2:44][NH:43][CH2:42][C@H:41]2[OH:46])[C:33]=1[C:47]1[CH:52]=[CH:51][C:50]([O:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[CH:49][CH:48]=1>CN(C=O)C>[NH2:31][C:32]1[N:37]=[CH:36][N:35]=[C:34]([NH:38][CH2:39][C@@H:40]2[CH2:45][CH2:44][N:43]([C:1](=[O:4])[C:2]#[CH:3])[CH2:42][C@H:41]2[OH:46])[C:33]=1[C:47]1[CH:52]=[CH:51][C:50]([O:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[CH:49][CH:48]=1

Participants

6

Reactant 4

HCID 10110Propiolic AcidHCID 81531DiisopropylethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 71092775HCID 71092775, compound

Product 1

HCID 86721742HCID 86721742, compoundYield 23.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a 20 mL reaction vial was added propiolic acid (0.02 ml; 0.37 mmol; 1.10 eq.), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (171.33 mg; 0.67 mmol; 2.00 eq.) and ethyl-diisopropyl-amine (0.28 ml; 1.68 mmol; 5.00 eq.) and 1.0 mL DMF. The reaction was stirred at rt for 1 h. Then (3S,4S)-4-{[6-Amino-5-(4-phenoxy-phenyl)-pyrimidin-4-ylamino]-methyl}-piperidin-3-ol hydrochloride (144.00 mg; 0.34 mmol; 1.00 eq.) in 1.0 mL DMF was added to the reaction mixture. The reaction mixture was stirred at rt overnight and then concentrated. The crude product was subjected to 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-yn-1-one as a white solid (35.2 mg, 18.6%). HPLC purity: 99%. MS: m/z=444 [M+H]+. 1H NMR (CD3OD) δ 8.24 (s, 1H), 7.10-7.46 (m, 9H), 4.36 (m, 2H), 4.00 (d, 1H), 3.74 (m, 1H), 3.52 (m, 1H), 3.25 (m, 1H), 3.00 (m, 1H), 2.64 (m, 1H), 1.76 (m, 2H), 1.30 (m, 1H).

Workup

  1. customTo a 20 mL reaction
  2. stirringThe reaction mixture was stirred at rt overnight
  3. concentrationconcentrated
  4. additionFractions containing the desired product
  5. waitlyophilized overnight

Sources & evidence

ORD record
ord-7178b29ab3fa430badc0284ad6899a6a
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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