Dimethylformamide → HCID 117777790, compound

HRID 1775891Notes

Reaction equation

HRID 1775891 reaction equation
[NH2:1][C@@H:2]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[CH:28][CH:27]=3)=[CH:22][N:21]=2)=[CH:16][CH:15]=1)[C:3]([N:5]1[CH2:8][CH:7]([C:9]([O:11][CH3:12])=[O:10])[CH2:6]1)=[O:4].[C:40]([C:44]1[S:48][C:47]([C:49](O)=[O:50])=[CH:46][CH:45]=1)([CH3:43])([CH3:42])[CH3:41].CN(C=O)C.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>>[C:40]([C:44]1[S:48][C:47]([C:49]([NH:1][C@@H:2]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:25]=[CH:24][C:23]([C:26]4[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[CH:30][CH:31]=4)=[CH:22][N:21]=3)=[CH:16][CH:15]=2)[C:3]([N:5]2[CH2:6][CH:7]([C:9]([O:11][CH3:12])=[O:10])[CH2:8]2)=[O:4])=[O:50])=[CH:46][CH:45]=1)([CH3:43])([CH3:41])[CH3:42]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 4583495-Tert-butylthiophene-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117740331HCID 117740331, compound

Product 1

HCID 117777790HCID 117777790, compoundYield 82.3%

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-methyl 1-(2-amino-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate (360 mg, 0.678 mmol) and 5-(tert-butyl)thiophene-2-carboxylic acid (125 mg, 0.678 mmol) in DMF (6 mL, 77 mmol) was added DIEA (0.47 mL, 2.71 mmol) and the mixture cooled to 0° C. HATU (284 mg, 0.746 mmol) was added portion-wise and the reaction stirred at room temperature for 1 h. The mixture was poured onto citric acid (70 mL of a 10% w/w aqueous solution) and extracted with EA (2×100 mL). The combined organic extracts were washed with brine (50 mL), dried over MgSO4 and solvents evaporated. Column chromatography (EA/iso-hexanes) gave 389 mg (82%) of (S)-methyl 1-(2-(5-(tert-butyl)thiophene-2-carboxamido)-3-(4-(5-(4-(heptyloxy)phenyl)pyrimidin-2-yl)phenyl)propanoyl)azetidine-3-carboxylate as a pale yellow solid. LCMS-ESI (m/z) calculated for C40H48N4O5S: 696.3. found 697.0 [M+H]+, tR=3.60 min (Method 6).

Workup

  1. additionThe mixture was poured onto citric acid (70 mL of a 10% w/w aqueous solution) and
  2. extractionextracted with EA (2×100 mL)
  3. washThe combined organic extracts were washed with brine (50 mL)
  4. dry with materialdried over MgSO4 and solvents
  5. customevaporated

Sources & evidence

ORD record
ord-b4e6ee762ebd41b4aef7e88de144b74e
Source dataset
uspto-grants-2016_02
Patent number
US09260427B2

Reaction notes

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