1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 131734245, compound

HRID 1499170Notes

Reaction equation

HRID 1499170 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([O:8][C@H:9]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=2[N:23]2[CH:27]=[CH:26][C:25]([CH3:28])=[N:24]2)[C:10]([F:13])([F:12])[F:11])[CH:5]=[C:4]([N:29]2[CH2:58][CH2:57][C:32]3([CH2:36][C@@H:35]([C:37]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[O:38])[N:34]([C:47]([O:49][CH2:50][C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)=[O:48])[CH2:33]3)[CH2:31][CH2:30]2)[N:3]=1.[CH3:59][C:60](O)([C:65]([F:68])([F:67])[F:66])[C:61]([F:64])([F:63])[F:62].CCN=C=NCCCN(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[NH2:1][C:2]1[N:3]=[C:4]([N:29]2[CH2:58][CH2:57][C:32]3([CH2:36][C@@H:35]([C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[O:38])[N:34]([C:47]([O:49][CH2:50][C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)=[O:48])[CH2:33]3)[CH2:31][CH2:30]2)[CH:5]=[C:6]([O:8][C@H:9]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([O:20][C:60]([CH3:59])([C:65]([F:68])([F:67])[F:66])[C:61]([F:64])([F:63])[F:62])=[O:19])=[CH:16][C:15]=2[N:23]2[CH:27]=[CH:26][C:25]([CH3:28])=[N:24]2)[C:10]([F:12])([F:11])[F:13])[N:7]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 739361,1,1,3,3,3-Hexafluoro-2-methylpropan-2-olHCID 117952517HCID 117952517, compound

Product 1

HCID 131734245HCID 131734245, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-[(1R)-1-[2-amino-6-[(2S)-2,3-bis(benzyloxycarbonyl)-3,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-yl]oxy-2,2,2-trifluoro-ethyl]-3-(3-methylpyrazol-1-yl)benzoic acid (80 mg, 0.1 mmol) in CH2Cl2 (4 mL) was added DMAP (73 mg, 0.6 mmol), (CF3)2MeCOH (108 mg, 0.6 mmol), followed by EDCI (114 mg, 0.6 mmol). The reaction mixture was stirred at RT for 12 h, diluted with CH2Cl2 and washed with water. The aqueous solution was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided dibenzyl (2S)-8-[2-amino-6-[(1R)-2,2,2-trifluoro-1-[2-(3-methylpyrazol-1-yl)-4-[2,2,2-trifluoro-1-methyl-1-(trifluoromethyl)ethoxy]carbonyl-phenyl]ethoxy]pyrimidin-4-yl]-3,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid.

Workup

  1. washwashed with water
  2. extractionThe aqueous solution was extracted with CH2Cl2
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record
ord-69babe235f144ff58fa8dbbf9748e5d2
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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