Diisopropylethylamine → HCID 67342269, compound

HRID 1401781Notes

Reaction equation

HRID 1401781 reaction equation
Cl.[CH3:2][C:3]1([CH3:27])[CH2:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]2[CH:8]=[C:7]([C:15]3[N:16]=[C:17]([N:20]4[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]4)[S:18][CH:19]=3)[CH:6]=[CH:5][C:4]1=2.C(OC([NH:35][C@@H:36]([CH2:40][CH2:41][O:42][Si](C(C)(C)C)(C)C)[C:37](O)=[O:38])=O)(C)(C)C.C(N(C(C)C)C(C)C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>C(Cl)Cl.CC(=O)OCC>[NH2:35][C@@H:36]([CH2:40][CH2:41][OH:42])[C:37]([NH:26][CH:23]1[CH2:24][CH2:25][N:20]([C:17]2[S:18][CH:19]=[C:15]([C:7]3[CH:6]=[CH:5][C:4]4[C:3]([CH3:27])([CH3:2])[CH2:12][CH2:11][C:10]([CH3:13])([CH3:14])[C:9]=4[CH:8]=3)[N:16]=2)[CH2:21][CH2:22]1)=[O:38]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 2724699PyBOPHCID 57699958HCID 57699958, compoundHCID 68381095HCID 68381095, compound

Product 1

HCID 67342269HCID 67342269, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

50 mg (0.12 mmol) of 1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-ylamine hydrochloride and 44 mg (0.13 mmol) of (S)-2-tert-butoxycarbonylamino-4-(tert-butyldimethylsilanyloxy)butyric acid (preparation analogous to Tetrahedron, 2005, vol. 61, #43 p. 10277-10284) were dissolved in 1 ml of DCM together with 50 μl (0.29 mmol) of N-ethyldiisopropylamine and stirred at 0° C. for 5 min. 73 mg (0.14 mmol) of benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate and 50 μl (0.29 mmol) of ethyldiisopropylamine were then added. The mixture was stirred further at 0° C. for 1 h, diluted with EA and washed by shaking with water and a saturated sodium hydrogencarbonate solution and a saturated sodium chloride solution. The organic phase was dried over sodium sulfate, filtered and evaporated. A 1.25 M HCl solution in methanol was then added to the residue, and the mixture was stirred for 1 h. The methanolic solution was evaporated, and the product was purified by means of preparative HPLC. The product is in the form of the hydrochloride.

Workup

  1. stirringThe mixture was stirred further at 0° C. for 1 h
  2. washwashed
  3. stirringby shaking with water
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. additionA 1.25 M HCl solution in methanol was then added to the residue
  8. stirringthe mixture was stirred for 1 h
  9. customThe methanolic solution was evaporated
  10. customthe product was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-73f46ac2f22e4a85b7d6d3aefe902a0a
Source dataset
uspto-grants-2014_12
Patent number
US08907098B2

Reaction notes

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