Diisopropylethylamine → 3-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

HRID 1850548Notes

Reaction equation

HRID 1850548 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:25](=[O:29])[N:26]([CH3:28])[CH3:27])[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=C[CH:44]=[CH:45][C:40]=2N=N1.[CH:54](N(CC)C(C)C)(C)C.[CH:63]12[N:70]([C:71]([OH:73])=[O:72])[CH:67]([CH2:68][CH2:69]1)[CH2:66][NH:65][CH2:64]2>CN(C=O)C.CCOC(C)=O>[C:45]([O:72][C:71]([N:70]1[CH:63]2[CH2:69][CH2:68][CH:67]1[CH2:66][N:65]([C:20]([C:19]1[CH:18]=[N:17][C:16]([NH:15][C:12]3[N:13]=[CH:14][C:9]4[CH:8]=[C:7]([C:25](=[O:29])[N:26]([CH3:27])[CH3:28])[N:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)[C:10]=4[N:11]=3)=[CH:24][CH:23]=1)=[O:22])[CH2:64]2)=[O:73])([CH3:44])([CH3:40])[CH3:54]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222733513,8-Diaza-bicyclo[3.2.1]octane-8-carboxylic acidHCID 583154726-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid

Product 1

HCID 673560653-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridine-3-carbonyl]-3,8-diaza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid (400 mg, 1.01 mmol) in DMF (5 mL) was added O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 580 mg, 1.53 mmol, 1.5 equiv) and N,N-diisopropylethylamine (0.55 mL, 3.0 equiv) and the resulting mixture stirred at room temperature for 5 minutes. To the reaction mixture was added 3,8-Diaza-bicyclo[3.2.1]octane-8-carboxylic acid Pert-butyl ester (250 mg, 1.18 mmol. 1.1 eq). The resulting mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted in EtOAc, washed with 0.5M HCl, water, dried over Na2SO4, filtered and concentrated. Material was immediately used in next step without further purification. MS: (M+H)=589.7

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 30 minutes
  2. washwashed with 0.5M HCl, water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customMaterial was immediately used in next step without further purification

Sources & evidence

ORD record
ord-bf157198fe7748929b642636dddef7c1
Source dataset
uspto-grants-2015_02
Patent number
US08957074B2

Reaction notes

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