Diisopropylethylamine → tert-Butyl{(1R,2R)-3,3-difluoro-2-[({5-methyl-4-[6-(trimethoxymethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophen-2-yl}carbonyl)amino]cyclohexyl}carbamate

HRID 1842604Notes

Reaction equation

HRID 1842604 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7](O)=[O:8])=[CH:4][C:3]=1[C:10]1[CH:11]=[N:12][N:13]2[CH:18]=[C:17]([C:19]([O:24][CH3:25])([O:22][CH3:23])[O:20][CH3:21])[CH:16]=[N:15][C:14]=12.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:53][C@H:54]1[C:59]([F:61])([F:60])[CH2:58][CH2:57][CH2:56][C@H:55]1[NH:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66].C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:65]([O:64][C:63](=[O:69])[NH:62][C@@H:55]1[CH2:56][CH2:57][CH2:58][C:59]([F:61])([F:60])[C@@H:54]1[NH:53][C:7]([C:5]1[S:6][C:2]([CH3:1])=[C:3]([C:10]2[CH:11]=[N:12][N:13]3[CH:18]=[C:17]([C:19]([O:24][CH3:25])([O:20][CH3:21])[O:22][CH3:23])[CH:16]=[N:15][C:14]=23)[CH:4]=1)=[O:8])([CH3:66])([CH3:68])[CH3:67]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 59603811tert-Butyl ((1R,2R)-2-amino-3,3-difluorocyclohexyl)carbamateHCID 673459195-Methyl-4-[6-(trimethoxymethyl)pyrazolo [1,5-a]pyrimidin-3-yl]thiophene-2-carboxylic acid

Product 1

HCID 131732414tert-Butyl{(1R,2R)-3,3-difluoro-2-[({5-methyl-4-[6-(trimethoxymethyl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophen-2-yl}carbonyl)amino]cyclohexyl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Methyl-4-[6-(trimethoxymethyl)pyrazolo [1,5-a]pyrimidin-3-yl]thiophene-2-carboxylic acid (41.0 mg, 0.113 mmol) and BOP (59.9 mg, 0.135 mmol) were dissolved in DMF (752 μL) and stirred at room temperature for 5 min. To the reaction solution was added tert-butyl [(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (31.1 mg, 0.124 mmol) and diisopropylethyl amine (59.1 μL, 0.338 mmol) and the reaction stirred at room temperature for 2 h. The reaction was then concentrated under reduced pressure and purified by column chromatography (0-60% EtOAc/DCM) to afford the title compound (quantitative yield). LRMS (APCI) calc'd for (C27H35F2N5O6S) [M+H]+, 596.2; found 596.1.

Workup

  1. stirringthe reaction stirred at room temperature for 2 h
  2. concentrationThe reaction was then concentrated under reduced pressure
  3. custompurified by column chromatography (0-60% EtOAc/DCM)

Sources & evidence

ORD record
ord-739922d59dbb456f8fa4b3462c42ab2c
Source dataset
uspto-grants-2015_02
Patent number
US08946237B2

Reaction notes

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