Diisopropylethylamine → (2R,5S)-4-{2-[6-(1,1-Difluoro-butyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475515Notes

Reaction equation

HRID 1475515 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:34]([O:38][C:39]([N:41]1[CH2:46][C@H:45]([CH2:47][N:48]2[CH2:53][CH2:52][O:51][CH2:50][C@H:49]2[CH3:54])[N:44]([CH2:55][C:56](O)=[O:57])[CH2:43][C@H:42]1[CH3:59])=[O:40])([CH3:37])([CH3:36])[CH3:35].[F:60][C:61]([C:66]1[CH:67]=[C:68]2[NH:74][CH2:73][C:72]([CH3:76])([CH3:75])[C:69]2=[N:70][CH:71]=1)([F:65])[CH2:62][CH2:63][CH3:64]>CN(C=O)C>[C:34]([O:38][C:39]([N:41]1[CH2:46][C@H:45]([CH2:47][N:48]2[CH2:53][CH2:52][O:51][CH2:50][C@H:49]2[CH3:54])[N:44]([CH2:55][C:56]([N:74]2[C:68]3[C:69](=[N:70][CH:71]=[C:66]([C:61]([F:65])([F:60])[CH2:62][CH2:63][CH3:64])[CH:67]=3)[C:72]([CH3:75])([CH3:76])[CH2:73]2)=[O:57])[CH2:43][C@H:42]1[CH3:59])=[O:40])([CH3:36])([CH3:37])[CH3:35]

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 709805096-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridineHCID 70980770(2R,5S)-4-Carboxymethyl-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 70981092(2R,5S)-4-{2-[6-(1,1-Difluoro-butyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 52.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (3.8 g, 9.9 mmol) and DIPEA (2.4 mL, 13.3 mmol) were added to a solution of (2R,5S)-4-carboxymethyl-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (1.7 g, 6.7 mmol) and 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine (1.6 g, 6.7 mmol) in DMF (10 mL). The reaction was stirred at room temperature for 16 h and then partitioned between saturated aqueous NaHCO3 and EtOAc. The organic phase was separated, washed with brine (3×), dried over MgSO4 and concentrated in vacuo. Chromatography (70% EtOAc in Petrol) gave the title compound (2.1 g) as a yellow solid. MS: [M+H]+=594.

Workup

  1. custompartitioned between saturated aqueous NaHCO3 and EtOAc
  2. customThe organic phase was separated
  3. washwashed with brine (3×)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-626538105ffb4e4e9c225701f5d970a0
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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