Diisopropylethylamine → 5-(2-Amino-6-{2-[(S)-3-tert-butoxycarbonylamino-1-(morpholine-4-carbonyl) propylcarbamoyl]ethylsulfanyl}pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester

HRID 1811732Notes

Reaction equation

HRID 1811732 reaction equation
F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:34]([O:38][C:39](=[O:53])[NH:40][CH2:41][CH2:42][C@H:43]([NH2:52])[C:44]([N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1)=[O:45])([CH3:37])([CH3:36])[CH3:35].[C:54]([O:58][C:59](=[O:81])[C:60]1[CH:65]=[C:64]([C:66]2[CH:71]=[C:70]([S:72][CH2:73][CH2:74][C:75](O)=[O:76])[N:69]=[C:68]([NH2:78])[N:67]=2)[C:63]([CH3:79])=[CH:62][C:61]=1[CH3:80])([CH3:57])([CH3:56])[CH3:55]>CN(C)C=O>[C:54]([O:58][C:59](=[O:81])[C:60]1[CH:65]=[C:64]([C:66]2[CH:71]=[C:70]([S:72][CH2:73][CH2:74][C:75](=[O:76])[NH:52][C@H:43]([C:44]([N:46]3[CH2:47][CH2:48][O:49][CH2:50][CH2:51]3)=[O:45])[CH2:42][CH2:41][NH:40][C:39]([O:38][C:34]([CH3:37])([CH3:35])[CH3:36])=[O:53])[N:69]=[C:68]([NH2:78])[N:67]=2)[C:63]([CH3:79])=[CH:62][C:61]=1[CH3:80])([CH3:57])([CH3:56])[CH3:55]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592246645-[2-Amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethyl-benzoic acid tert-butyl esterHCID 59224697((S)-3-amino-4-morpholin-4-yl-4-oxobutyl)carbamic acid tert-butyl ester

Product 1

HCID 592246665-(2-Amino-6-{2-[(S)-3-tert-butoxycarbonylamino-1-(morpholine-4-carbonyl) propylcarbamoyl]ethylsulfanyl}pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl esterYield 100.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (58 mg, 0.149 mmol), and diisopropylethylamine (43 μl, 0.247 mmol) were added at room temperature to an N,N-dimethylformamide solution (1.0 ml) of ((S)-3-amino-4-morpholin-4-yl-4-oxobutyl)carbamic acid tert-butyl ester (44 mg) obtained in Step 2 above and 5-[2-amino-6-(2-carboxyethylsulfanyl)pyrimidin-4-yl]-2,4-dimethyl-benzoic acid tert-butyl ester (50.3 mg) obtained in Step 1 of Example 2-1. The reaction solution was stirred for 16 hours, and then concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield 5-(2-amino-6-{2-[(S)-3-tert-butoxycarbonylamino-1-(morpholine-4-carbonyl)propylcarbamoyl]ethylsulfanyl}pyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (84 mg) as a pale yellow oily material.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1)

Sources & evidence

ORD record
ord-c4237e27e68d4044be24572deaf15f16
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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