Ammonia → HCID 59828868, compound

HRID 1191153Notes

Reaction equation

HRID 1191153 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8](C(=O)C(F)(F)F)[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:28]=[C:29]([NH:32][C:33]([CH:35]3[CH2:37][CH2:36]3)=[O:34])[S:30][CH:31]=2)=[CH:23][CH:22]=1.N>CO>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[C:3]=1[NH:19][CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[N:28]=[C:29]([NH:32][C:33]([CH:35]3[CH2:37][CH2:36]3)=[O:34])[S:30][CH:31]=2)=[CH:25][CH:26]=1

Participants

4

Reactant 2

HCID 222Ammonia2×HCID 86624187HCID 86624187, compound

Product 1

HCID 59828868HCID 59828868, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To 7-chloro-6-{4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamino}-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.310 g, 5.648 mmol) at room temperature, add 2M ammonia in methanol (18 mL). After stirring for 30 min, add 7M ammonia in methanol (124 mL) to the reaction mixture. After stirring at room temperature overnight, concentrate the reaction mixture in vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM and load the solution on to a RediSep® column (40 g). Purify by preparative liquid chromatography (0:1 to 1:9 2M ammonia in methanol/DCM over 33 min, 1:9 to 1:4 2M ammonia in methanol/DCM over 33 min; 35 mL/min) to afford 7-chloro-6-{4-[2-(cyclopropanecarbonyl-amino)-thiazol-4-yl]-benzylamino}-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.140 g, 55%) as a white foam. MS (ES+) m/z: 453.1 (M+H)+.

Workup

  1. stirringAfter stirring at room temperature overnight
  2. concentrationconcentrate the reaction mixture in vacuo
  3. washelute the residue through a SCX column (20 g)
  4. dissolutionDissolve the residue in DCM
  5. customPurify by preparative liquid chromatography (0:1 to 1:9 2M ammonia in methanol/DCM over 33 min, 1:9 to 1:4 2M ammonia in methanol/DCM over 33 min; 35 mL/min)

Sources & evidence

ORD record
ord-ed9ca956d85c4ac79dc67a6b2acdfdb8
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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