Diisopropylethylamine → HCID 58255041, compound

HRID 536365Notes

Reaction equation

HRID 536365 reaction equation
[Cl:1][C:2]1[C:3]([NH:23][C:24]2[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[C:12]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:11][C:10]=2[F:22])=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OC([N:70]1[CH2:73][CH:72]([C:74](O)=[O:75])[CH2:71]1)=O)(C)(C)C>CN(C=O)C.CO.Cl>[NH:70]1[CH2:73][CH:72]([C:74]([N:19]2[CH2:18][CH2:17][CH:16]([C:12]3[CH:11]=[C:10]([F:22])[C:9]([NH:8][C:5]4[N:4]=[C:3]([NH:23][C:24]5[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=5)[C:2]([Cl:1])=[CH:7][N:6]=4)=[CH:14][C:13]=3[CH3:15])[CH2:21][CH2:20]2)=[O:75])[CH2:71]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 446126165-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

Product 1

HCID 58255041HCID 58255041, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-chloro-N2-(2-fluoro-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (0.12 mmol), di-isopropylethylamine (50 uL, 0.36 mmol) and HATU (55 mg, 0.14 mmol) in DMF (1.5 mL) was added 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (29 mg, 0.14 mmol). After stirring at room temperature for 4 hours, the mixture was diluted with methanol (1 mL) and conc. aqueous HCl (1 mL). The mixture was stirred at 50° C. for 30 min. The mixture was filtered and purified by preparative RP-HPLC to give azetidin-3-yl(4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-5-fluoro-2-methylphenyl)piperidin-1-yl)methanone as white solid. 1H NMR (400 MHz, MeOD-d4) δ 8.08 (s, 1H), 7.68 (d, 2H), 7.04 (d, 2H), 6.26 (s, 1H), 4.74-4.68 (m, 2H), 4.39-4.35 (m, 1H), 4.29-4.24 (m, 2H), 4.11-4.07 (m, 1H), 3.74-3.71 (m, 1H), 3.25-3.24 (m, 1H), 3.07-3.04 (m, 1H), 2.87-2.80 (m, 1H), 2.33 (s, 3H), 2.28 (s, 3H), 1.87-1.84 (m, 2H), 1.66-1.56 (m, 2H); ESMS m/z 499.2 (M+H+).

Workup

  1. stirringThe mixture was stirred at 50° C. for 30 min
  2. filtrationThe mixture was filtered
  3. custompurified by preparative RP-HPLC

Sources & evidence

ORD record
ord-a70dd8082d794481ade1e3d01a788123
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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