Diisopropylethylamine → N-[(S)-1-(1-Cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide

HRID 1664720Notes

Reaction equation

HRID 1664720 reaction equation
CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:35][C:36]1([C:39]#[N:40])[CH2:38][CH2:37]1.[CH2:41]1[C:45]2([CH2:50][CH2:49][N:48]([C:51]([NH:53][C@@H:54]([CH2:58][C:59]([F:68])([F:67])[CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[C:55](O)=[O:56])=[O:52])[CH2:47][CH2:46]2)[CH2:44][CH2:43][CH2:42]1>CN(C=O)C>[C:39]([C:36]1([NH:35][C:55]([C@@H:54]([NH:53][C:51]([N:48]2[CH2:47][CH2:46][C:45]3([CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:50][CH2:49]2)=[O:52])[CH2:58][C:59]([F:67])([F:68])[CH2:60][C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[O:56])[CH2:38][CH2:37]1)#[N:40]

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 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 66661164(S)-2-[(8-Azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid

Product 1

HCID 24996348N-[(S)-1-(1-Cyanocyclopropylcarbamoyl)-3,3-difluoro-4-phenylbutyl]-8-azaspiro[4.5]decane-8-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (331 μl, 252 mg, 1.95 mmol, 4 eq.), HATU (185 mg, 0.49 mmol, 1 eq.) and 1-aminocyclopropanecarbonitrile hydrochloride (58 mg, 0.49 mmol, 1 eq.) were added successively to a solution of the (S)-2-[(8-azaspiro[4.5]decane-8-carbonyl)amino]-4,4-difluoro-5-phenylpentanoic acid obtained as a crude product (192 mg, 0.49 mmol) in 10 ml of DMF. The reaction mixture was stirred at RT overnight and, the next day, concentrated under reduced pressure. The residue thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The title compound was obtained in the form of a colorless crystalline material.

Workup

  1. concentrationthe next day, concentrated under reduced pressure
  2. customThe residue thus obtained
  3. customwas purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA)

Sources & evidence

ORD record
ord-de68fad26a344dddb9e252b21ebdf6af
Source dataset
uspto-grants-2011_10
Patent number
US08039480B2

Reaction notes

Loading…