Propylphosphonic anhydride → (1-{4-Bromo-6-[(triisopropylsilanyl)-ethynyl]-pyridin-2-ylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester

HRID 923660

Reaction equation

HRID 923660 reaction equation
C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC.[Br:19][C:20]1[CH:25]=[C:24]([C:26]#[C:27][Si:28]([CH:35]([CH3:37])[CH3:36])([CH:32]([CH3:34])[CH3:33])[CH:29]([CH3:31])[CH3:30])[N:23]=[C:22]([NH2:38])[CH:21]=1.[CH3:39][N:40]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH:41]([CH3:45])[C:42](O)=[O:43].C(=O)([O-])O.[Na+]>CCOC(C)=O.N1C=CC=CC=1>[C:49]([O:48][C:46](=[O:47])[N:40]([CH:41]([C:42](=[O:43])[NH:38][C:22]1[CH:21]=[C:20]([Br:19])[CH:25]=[C:24]([C:26]#[C:27][Si:28]([CH:32]([CH3:34])[CH3:33])([CH:35]([CH3:37])[CH3:36])[CH:29]([CH3:31])[CH3:30])[N:23]=1)[CH3:45])[CH3:39])([CH3:50])([CH3:51])[CH3:52]

Participants

7

Reactant 4

HCID 111923Propylphosphonic anhydrideHCID 516892Sodium BicarbonateHCID 44368572-(((Tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 1233890784-Bromo-6-[2-[tris(propan-2-yl)silyl]ethynyl}pyridin-2-amine

Product 1

HCID 123968434(1-{4-Bromo-6-[(triisopropylsilanyl)-ethynyl]-pyridin-2-ylcarbamoyl}-ethyl)-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (70 ml of a 50 wt.-% solution in EtOAc, 118 mmol) is added to a mixture of 4-bromo-6-{2-[tris(propan-2-yl)silyl]ethynyl}pyridin-2-amine B1 (10.4 g, 29.5 mmol), 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoic acid (12 g, 59 mmol) and pyridine (20 ml) at −20° C. The mixture is stirred for 3 h at that temperature. 200 ml of a saturated aqueous sodium hydrogencarbonate solution is added and the mixture extracted with EtOAc. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by NP chromatography. Yield: 11.1 g (70%). HPLC-MS: M+H=538/540; tR=.2.05 min (METHOD—1).

Workup

  1. extractionthe mixture extracted with EtOAc
  2. dry with materialThe combined organic layers are dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe product is purified by NP chromatography
  5. custom2.05 min (METHOD—1)

Sources & evidence

ORD record
ord-0d8322577e0848fcbf4e8f05bf79edc5
Source dataset
uspto-grants-2016_03
Patent number
US09278978B2

Linked notes

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