Diisopropylethylamine → (5R,8S)-7-((S)-2-{(S)-2-Cyclohexyl-2-[((S)-1-isopropyl-piperidine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

HRID 1893098Notes

Reaction equation

HRID 1893098 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH2:7][CH2:6][C@H:5]1[C:10]([OH:12])=O)([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:37][O:38][C:39]([C@@H:41]1[CH2:52][C@:44]2([C:49]([CH3:51])([CH3:50])[C:45]32[CH2:48][CH2:47][CH2:46]3)[CH2:43][N:42]1[C:53](=[O:70])[C@@H:54]([NH:59][C:60](=[O:69])[C@@H:61]([NH2:68])[CH:62]1[CH2:67][CH2:66][CH2:65][CH2:64][CH2:63]1)[C:55]([CH3:58])([CH3:57])[CH3:56])=[O:40].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:37][O:38][C:39]([C@@H:41]1[CH2:52][C@:44]2([C:49]([CH3:50])([CH3:51])[C:45]32[CH2:48][CH2:47][CH2:46]3)[CH2:43][N:42]1[C:53](=[O:70])[C@@H:54]([NH:59][C:60](=[O:69])[C@H:61]([CH:62]1[CH2:63][CH2:64][CH2:65][CH2:66][CH2:67]1)[NH:68][C:10]([C@@H:5]1[CH2:6][CH2:7][CH2:8][CH2:9][N:4]1[CH:1]([CH3:2])[CH3:3])=[O:12])[C:55]([CH3:58])([CH3:57])[CH3:56])=[O: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 49759876N-isopropyl-L-2-piperidinecarboxylic acidHCID 59533249(5R,8S)-7-[(S)-2-((S)-2-Amino-2-cyclohexyl-acetylamino)-3,3-dimethyl-butyryl]-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

Product 1

HCID 59533292(5R,8S)-7-((S)-2-{(S)-2-Cyclohexyl-2-[((S)-1-isopropyl-piperidine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-1-isopropyl-piperidine-2-carboxylic acid (0.497 g; 2.90 mmol) and HATU (1.65 g; 4.35 mmol) in DCM (100 mL) was cooled to 0° C. and (5R,8S)-7-[(S)-2-((S)-2-Amino-2-cyclohexyl-acetylamino)-3,3-dimethyl-butyryl]-10,10-dimethyl-7-aza-dispiro[3.0.4.1]decane-8-carboxylic acid methyl ester (1.65 g; 2.90 mmol) and DIPEA (2.98 mL; 17.4 mmol) were added. The reaction mixture was stirred for 3 h at room temperature quenched with saturated aqueous bicarbonate. The aq. phase was extracted twice with DCM, the combined organic phases dried with Na2SO4, filtered and the solvent was removed in vacuo. The product was purified by preparative HPLC (method L) to yield the title compound. LC-MS (method E): Rt=1.62 min; M/z=629 [M+]; HPLC (method A3): Rt=5.01 min

Workup

  1. customquenched with saturated aqueous bicarbonate
  2. extractionThe aq. phase was extracted twice with DCM
  3. dry with materialthe combined organic phases dried with Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. customThe product was purified by preparative HPLC (method L)

Sources & evidence

ORD record
ord-c376afe0ebf34705a5c088e2591c25cb
Source dataset
uspto-grants-2013_08
Patent number
US08512690B2

Reaction notes

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