Propiolic Acid → HCID 86721738, compound

HRID 1522098Notes

Reaction equation

HRID 1522098 reaction equation
Cl.[CH2:2]1[C:5]2([CH2:8][CH:7]([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)[CH2:6]2)[CH2:4][NH:3]1.CCN(C(C)C)C(C)C.[C:39](O)(=[O:42])[C:40]#[CH:41].C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>C(Cl)Cl>[NH2:29][C:14]1[N:13]=[CH:12][N:11]=[C:10]([NH:9][CH:7]2[CH2:8][C:5]3([CH2:4][N:3]([C:39](=[O:42])[C:40]#[CH:41])[CH2:2]3)[CH2:6]2)[C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 10110Propiolic AcidHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 86721739HCID 86721739, compound

Product 1

HCID 86721738HCID 86721738, compoundYield 32.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a microwave vial containing N-(2-Aza-spiro[3.3]hept-6-yl)-5-(4-phenoxy-phenyl)-pyrimidine-4,6-diamine hydrochloride (80.00 mg; 0.20 mmol; 1.00 eq.) in DCM (1.00 ml) was added DIPEA (0.16 ml; 0.98 mmol; 5.00 eq.) and propiolic acid (24.20 μl; 0.39 mmol; 2.00 eq.) followed by 2,4,6-Tripropyl-[1,3,5,2,4,6]trioxatriphosphinane 2,4,6-trioxide (0.12 ml; 0.29 mmol; 1.50 eq.). The reaction was stirred at rt for 1 h before it was concentrated and purified by preparative HPLC (0.1% TFA-H2O/ACN). Fractions containing the desired product were combined and lyophilized overnight to afford 1-(6-((6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl)amino)-2-azaspiro[3.3]heptan-2-yl)prop-2-yn-1-one as a white solid (27.8 mg, 26.1%). HPLC purity: 99%. MS: m/z=426 [M+H]+. 1H NMR (CD3OD) δ 8.25 (s, 1H), 7.18-7.49 (m, 9H), 4.32 (d, 1H), 4.09 (d, 2H), 3.89 (d, 1H), 2.60 (m, 2H), 2.29 (m, 2H).

Workup

  1. concentrationwas concentrated
  2. custompurified by preparative HPLC (0.1% TFA-H2O/ACN)
  3. additionFractions containing the desired product
  4. waitlyophilized overnight

Sources & evidence

ORD record
ord-0d682292c8fa430cb89af201c20c57d2
Source dataset
uspto-grants-2015_07
Patent number
US09073947B2

Reaction notes

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